S2k guidelines for the therapy of pathological scars (hypertrophic scars and keloids) – Update 2020 - Nast, Alexander; Gauglitz, Gerd; Lorenz, Kerstin; Metelmann, Hans-Robert; Paasch, Uwe; Strnad, Vratislav; Weidmann, Michael; Werner, Ricardo Niklas; Bauerschmitz, Jürgen (Journal der Deutschen Dermatologischen Gesellschaft, 2020)
CRIS-Team Scopus Importer:2020-10-16

S2k guidelines for the treatment of pemphigus vulgaris/foliaceus and bullous pemphigoid: 2019 update - Schmidt, Enno; Sticherling, Michael; Sárdy, Miklós; Eming, Rüdiger; Goebeler, Matthias; Hertl, Michael; Hofmann, Silke C.; Hunzelmann, Nicolas; Kern, Johannes S.; Kramer, Harald; Nast, Alexander; Orzechowski, Hans Dieter; et al. (Journal der Deutschen Dermatologischen Gesellschaft, 2020)
CRIS-Team Scopus Importer:2020-05-26

S2k guidelines for the treatment of pemphigus vulgaris/foliaceus and bullous pemphigoid - Eming, Ruediger; Sticherling, Michael; Hofmann, Silke C.; Hunzelmann, Nicolas; Kern, Johannes S.; Kramer, Harald; Pfeiffer, Christiane; Schuster, Volker; Zillikens, Detlef; Goebeler, Matthias; Hertl, Michael; Nast, Alexander; et al. (Journal der Deutschen Dermatologischen Gesellschaft, 2015)
EVALuna2:19564

S2k guidelines for the treatment of psoriasis in children and adolescents – Short version part 1 - Eisert, Lisa; Augustin, Matthias; Bach, Sabine; Dittmann, Martin; Eiler, Renate; Fölster-Holst, Regina; Gerdes, Sascha; Hamm, Henning; Höger, Peter; Horneff, Gerd; von Kiedrowski, Ralph; Philipp, Sandra; et al. (Journal der Deutschen Dermatologischen Gesellschaft, 2019)
The present guidelines are aimed at residents and board-certified physicians in the fields of dermatology, pediatrics, pediatric dermatology and pediatric rheumatology as well as policymakers and insurance funds. They were developed by dermatologists and pediatric dermatologists in collaboration with pediatric rheumatologists using a formal consensus process (S2k). The guidelines highlight topics such as disease severity, quality of life, treatment goals as well as problems associated with off-label drug therapy in children. Trigger factors and diagnostic aspects are discussed. The primary focus is on the various topical, systemic and UV-based treatment options available and includes recommendations for use and treatment algorithms. Other aspects addressed herein include vaccinations in children and adolescents with psoriasis as well as various disease subtypes such as guttate psoriasis, diaper psoriasis, pustular psoriasis and psoriatic arthritis. Finally, we also provide recommendations for imaging studies and the diagnostic workup to rule out tuberculosis prior to initiating systemic treatment. Note: This article constitutes part 1 of the Sk2 guidelines for the treatment of psoriasis in children and adolescents. Part 2 will be published in the next issue. It contains chapters on UV therapy, systemic treatment, tonsillectomy and antibiotics, vaccinations, guttate psoriasis, psoriatic arthritis, complementary medicine, as well as imaging studies and diagnostic workup to rule out tuberculosis prior to systemic treatment.
CRIS-Team Scopus Importer:2019-08-30

S2k guidelines for the treatment of psoriasis in children and adolescents - Short version part 2. - Eisert, Lisa; Augustin, Matthias; Bach, Sabine; Dittmann, Martin; Eiler, Renate; Foelster-Holst, Regina; Gerdes, Sascha; Hamm, Henning; Hoeger, Peter; Horneff, Gerd; Von Kiedrowski, Ralph; Philipp, Sandra; et al. (Journal der Deutschen Dermatologischen Gesellschaft, 2019)
The present guidelines are aimed at residents and board-certified physicians in the fields of dermatology, pediatrics, pediatric dermatology and pediatric rheumatology as well as policymakers and insurance funds. They were developed by dermatologists and pediatric dermatologists in collaboration with pediatric rheumatologists using a formal consensus process (S2k). The guidelines highlight topics such as disease severity, quality of life, treatment goals as well as problems associated with off-label drug therapy in children. Trigger factors and diagnostic aspects are discussed. The primary focus is on the various topical, systemic and UV-based treatment options available and includes recommendations for use and treatment algorithms. Other aspects addressed herein include vaccinations in children and adolescents with psoriasis as well as various disease subtypes such as guttate psoriasis, diaper psoriasis, pustular psoriasis and psoriatic arthritis. Finally, we also provide recommendations for imaging studies and the diagnostic workup to rule out tuberculosis prior to initiating systemic treatment. Note: This article constitutes part 2 of the Sk2 guidelines for the treatment of psoriasis in children and adolescents. Part 1 was published in last month's issue. It contained introductory remarks and addressed aspects of diagnosis and topical treatment.
EVALuna2:212834

S2k-Leitlinie Therapie pathologischer Narben (hypertrophe Narben und Keloide) –Update 2020 - Nast, Alexander; Gauglitz, Gerd; Lorenz, Kerstin; Metelmann, Hans Robert; Paasch, Uwe; Strnad, Vratislav; Weidmann, Michael; Werner, Ricardo Niklas; Bauerschmitz, Jürgen (Journal der Deutschen Dermatologischen Gesellschaft, 2021)
CRIS-Team Scopus Importer:2021-02-26

S2k-Leitlinie zur Diagnostik und Therapie des kutanen Lupus erythematodes – Teil 1: Klassifikation, Diagnostik, Prävention und Aktivitätsscores - Worm, Margitta; Zidane, Miriam; Eisert, Lisa; Fischer-Betz, Rebecca; Foeldvari, Ivan; Günther, Claudia; Iking-Konert, Christof; Kreuter, Alexander; Müller-Ladner, Ulf; Nast, Alexander; Ochsendorf, Falk; Schneider, Matthias; et al. (Journal der Deutschen Dermatologischen Gesellschaft, 2021)
CRIS-Team Scopus Importer:2021-09-17

S2k-Leitlinie zur Therapie der Psoriasis bei Kindern und Jugendlichen – Kurzfassung Teil 1 - Eisert, Lisa; Augustin, Matthias; Bach, Sabine; Dittmann, Martin; Eiler, Renate; Fölster-Holst, Regina; Gerdes, Sascha; Hamm, Henning; Höger, Peter; Horneff, Gerd; von Kiedrowski, Ralph; Philipp, Sandra; et al. (Journal der Deutschen Dermatologischen Gesellschaft, 2019)
CRIS-Team Scopus Importer:2019-08-30

S2k-Leitlinie zur Therapie der Psoriasis bei Kindern und Jugendlichen - Kurzfassung Teil 2. - Eisert, Lisa; Augustin, Matthias; Bach, Sabine; Dittmann, Martin; Eiler, Renate; Fölster-Holst, Regina; Gerdes, Sascha; Hamm, Henning; Höger, Peter; Horneff, Gerd; von Kiedrowski, Ralph; Philipp, Sandra; et al. (Journal der Deutschen Dermatologischen Gesellschaft, 2019)
Diese Leitlinie richtet sich an Assistenz- und Fachärzte der Dermatologie, Pädiatrie, Kinderdermatologie und Kinderrheumatologie sowie an Kostenträger und politische Entscheidungsgremien. Die Leitlinie wurde im formellen Konsensusverfahren (S2k) von Dermatologen und Kinderdermatologen unter Einbindung von Kinderrheumatologen erstellt. Die Leitlinie stellt einen Überblick über Schweregrad, Lebensqualität und Therapieziele mit Erläuterung der Off-Label-Problematik im Kindesalter dar. Es werden Diagnosestellung und Triggerfaktoren erläutert. Der Schwerpunkt der Leitlinie liegt auf der Darstellung der verschiedenen topischen Therapien, UV-Therapien und systemischen Therapieoptionen mit Abbildung der Empfehlungen zur Anwendung der Therapien sowie Therapiealgorithmen. Darüber hinaus wird im Kontext auf Impfungen bei Psoriasis im Kindesalter sowie auf verschiedene Sonderformen wie Psoriasis guttata, Windelpsoriasis, Psoriasis pustulosa und Psoriasisarthritis eingegangen. Auch werden Empfehlungen zu Tuberkulosediagnostik und Röntgenuntersuchung vor Systemtherapie gegebe
EVALuna2:212833

S2k-Leitlinie zur Therapie des Pemphigus vulgaris/foliaceus und des bullösen Pemphigoids: 2019 Update - Schmidt, Enno; Sticherling, Michael; Sárdy, Miklós; Eming, Rüdiger; Goebeler, Matthias; Hertl, Michael; Hofmann, Silke C.; Hunzelmann, Nicolas; Kern, Johannes S.; Kramer, Harald; Nast, Alexander; Orzechowski, Hans Dieter; et al. (Journal der Deutschen Dermatologischen Gesellschaft, 2020)
CRIS-Team Scopus Importer:2020-05-22

S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma"- update 2023, part 1: treatment of actinic keratosis, actinic cheilitis, cutaneous squamous cell carcinoma in situ (Bowen's disease), occupational disease and structures of care - Heppt, Markus; Leiter, Ulrike; Steeb, Theresa; Alter, Mareike; Amaral, Teresa; Bauer, Andrea; Bechara, Falk G.; Becker, Jürgen C.; Breitbart, Eckhard W.; Breuninger, Helmut; Diepgen, Thomas; Dirschka, Thomas; et al. (Journal der Deutschen Dermatologischen Gesellschaft, 2023)
Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline “actinic keratosis and cutaneous squamous cell carcinoma” was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to AK, actinic cheilitis, Bowen's disease, occupational disease and care structure
EVALuna2:541007

S3 guideline „actinic keratosis and cutaneous squamous cell carcinoma“ – update 2023, part 2: epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention - Leiter, Ulrike; Heppt, Markus; Steeb, Theresa; Alter, Mareike; Amaral, Teresa; Bauer, Andrea; Bechara, Falk G.; Becker, Jürgen C.; Breitbart, Eckhard W.; Breuninger, Helmut; Diepgen, Thomas; Dirschka, Thomas; et al. (Journal der Deutschen Dermatologischen Gesellschaft, 2023)
Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline “actinic keratosis and cutaneous squamous cell carcinoma” was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.
CRIS-Team Scopus Importer:2023-11-17

S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma (cSCC) - short version, part 2: epidemiology, surgical and systemic treatment of cSCC, follow-up, prevention and occupational disease - Leiter, Ulrike; Heppt, Markus; Steeb, Theresa; Amaral, Teresa; Bauer, Andrea; Becker, Juergen C.; Breitbart, Eckhardt; Breuninger, Helmut; Diepgen, Thomas; Dirschka, Thomas; Eigentler, Thomas; Flaig, Michael; et al. (Journal der Deutschen Dermatologischen Gesellschaft, 2020)
Actinic keratoses (AKs) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guidelines for actinic keratosis and cutaneous squamous cell carcinoma were developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guidelines are aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AKs and cSCC. The guidelines are also aimed at affected patients, their relatives, policy makers and insurance funds. In the second part, we will address aspects relating to epidemiology, etiology, surgical and systemic treatment of cSCC, follow-up and disease prevention, and discuss AKs and cSCC in the context of occupational disease regulations.
CRIS-Team WoS Importer:2020-04-17

S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma – short version, part 1: diagnosis, interventions for actinic keratoses, care structures and quality-of-care indicators - Heppt, Markus V.; Leiter, Ulrike; Steeb, Theresa; Amaral, Teresa; Bauer, Andrea; Becker, Jürgen C.; Breitbart, Eckhard; Breuninger, Helmut; Diepgen, Thomas; Dirschka, Thomas; Eigentler, Thomas; Flaig, Michael; et al. (Journal der Deutschen Dermatologischen Gesellschaft, 2020)
Actinic keratoses (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline “actinic keratosis and cutaneous squamous cell carcinoma” was developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guideline is aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AK and cSCC. The guideline is also aimed at affected patients, their relatives, policy makers and insurance funds. In the first part, we will address aspects relating to diagnosis, interventions for AK, care structures and quality-of-care indicators.
CRIS-Team Scopus Importer:2020-03-17

S3 guidelines: Epicutaneous patch testing with contact allergens and drugs – Short version, Part 1 - Mahler, Vera; Nast, Alexander; Bauer, Andrea; Becker, Detlef; Brasch, Jochen; Breuer, Kristine; Dickel, Heinrich; Drexler, Hans; Elsner, Peter; Geier, Johannes; John, Swen Malte; Kreft, Burkhard; et al. (Journal der Deutschen Dermatologischen Gesellschaft, 2019)
Epicutaneous patch testing is the diagnostic standard for the detection of allergic contact dermatitis. The present guidelines are aimed at residents and board-certified physicians in the fields of dermatology and allergology as well as other medical specialties involved in establishing the indication for patch testing and its execution in patients with contact dermatitis and other forms of delayed-type hypersensitivity. The target audience also includes other health care providers and insurance funds. Based on a systematic literature search and a formal consensus process (S3), the guidelines were developed by dermatologists in collaboration with pediatricians, occupational medicine physicians, nursing staff as well as patient representatives. The systematic methodological approach and appraisal of evidence upon which the recommendations are based are outlined in a separate method report that also contains evidence tables. The guidelines address general aspects of patch testing as well as medicolegal issues. The recommendations given relate to topics such as the indication for patch testing, informed patient consent, as well as the choice of test substances, test chambers and test site, duration of exposure, reading times and interpretation of test reactions. Furthermore, recommendations are provided with respect to endogenous and exogenous factors, specific patient groups (children, pregnant women, immunosuppressed individuals) as well as possible risks and adverse events associated with patch testing using contact allergens. Note: This publication is part 1 of the short version of the S3 guidelines for “Epicutaneous patch testing using contact allergens and drugs” (registry no. 013 – 018; date: March 20, 2019; valid until December 31, 2021). Part 2 of the short version will be published in the next issue. The long version of these guidelines can be accessed at www.awmf.org. The method report is available as online publication (https://www.awmf.org/leitlinien/detail/ll/013-018.html) and contains the evidence tables in its appendix.
CRIS-Team Scopus Importer:2019-10-29

S3-Leitlinie „Aktinische Keratose und Plattenepithelkarzinom der Haut“ – Kurzfassung, Teil 1: Diagnostik, Interventionen bei aktinischen Keratosen, Versorgungsstrukturen und Qualitätsindikatoren - Heppt, Markus V.; Leiter, Ulrike; Steeb, Theresa; Amaral, Teresa; Bauer, Andrea; Becker, Jürgen C.; Breitbart, Eckhard; Breuninger, Helmut; Diepgen, Thomas; Dirschka, Thomas; Eigentler, Thomas; Flaig, Michael; et al. (Journal der Deutschen Dermatologischen Gesellschaft, 2020)
Aktinische Keratosen (AK) sind häufige Hautveränderungen bei hellhäutigen Menschen mit dem Potenzial, in ein kutanes Plattenepithelkarzinom (PEK) überzugehen. Beide Erkrankungen können mit erheblicher Morbidität verbunden sein und stellen eine große Krankheitslast insbesondere in der älteren Bevölkerung dar. Um eine evidenzbasierte, klinische Entscheidungsfindung zu unterstützen, wurde die Leitlinie “Aktinische Keratose und Plattenepithelkarzinom der Haut” auf der Methodikebene S3 nach dem Regelwerk der AWMF entwickelt. Die Leitlinie richtet sich dabei an Dermatologen, Allgemeinmediziner, HNO-Ärzte, Chirurgen, Onkologen, Radiologen und Strahlentherapeuten in Klinik und Praxis sowie an andere medizinische Fachgebiete, die sich mit der Diagnose und Behandlung von Patienten mit AK und PEK befassen. Die Leitlinie richtet sich auch an betroffene Patienten, deren Angehörige, politische Entscheidungsträger und Versicherungsgesellschaften. In diesem Teil behandeln wir die Themen Diagnostik, Interventionen bei AK, Versorgungsstrukturen und Qualitätsindikatoren.
CRIS-Team Scopus Importer:2020-03-17

S3-Leitlinie "Aktinische Keratose und Plattenepithelkarzinom der Haut" - Kurzfassung, Teil 2: Epidemiologie, chirurgische und systemische Therapie des Plattenepithelkarzinoms, Nachsorge, Pravention und Berufskrankheit - Leiter, Ulrike; Heppt, Markus V.; Steeb, Theresa; Amaral, Teresa; Bauer, Andrea; Becker, Juergen C.; Breitbart, Eckhardt; Breuninger, Helmut; Diepgen, Thomas; Dirschka, Thomas; Eigentler, Thomas; Flaig, Michael; et al. (Journal der Deutschen Dermatologischen Gesellschaft, 2020)
Zusammenfassung Aktinische Keratosen (AK) sind haufige Hautveranderungen bei hellhautigen Menschen mit dem Potenzial, in ein kutanes Plattenepithelkarzinom (PEK) uberzugehen. Beide Erkrankungen konnen mit erheblicher Morbiditat verbunden sein und stellen eine gro ss e Krankheitslast insbesondere in der alteren Bevolkerung dar. Um eine evidenzbasierte, klinische Entscheidungsfindung zu unterstutzen, wurde die Leitlinie Aktinische Keratose und kutanes Plattenepithelkarzinom" auf der Methodikebene S3 nach dem Regelwerk der AWMF entwickelt. Die Leitlinie richtet sich dabei an Dermatologen, Allgemeinmediziner, HNO-Arzte, Chirurgen, Onkologen, Radiologen und Strahlentherapeuten in Klinik und Praxis sowie an andere medizinische Fachgebiete, die sich mit der Diagnose und Behandlung von Patienten mit AK und PEK befassen. Die Leitlinie richtet sich auch an betroffene Patienten, deren Angehorige, politische Entscheidungstrager und Versicherungsgesellschaften. In diesem Teil behandeln wir die Themen Epidemiologie, Atiologie, chirurgische und systemische Behandlung des PEK, Nachsorge des PEK, Pravention und Berufskrankheit durch AK und PEK.
CRIS-Team WoS Importer:2020-05-15

S3-Leitlinie “Aktinische Keratose und Plattenepithelkarzinom der Haut“ – Update 2023, Teil 1: Therapie der aktinischen Keratose, Morbus Bowen, Cheilitis actinica, berufsbedingte Erkrankung und Versorgungsstrukturen - Heppt, Markus; Leiter, Ulrike; Steeb, Theresa; Alter, Mareike; Amaral, Teresa; Bauer, Andrea; Bechara, Falk G.; Becker, Jürgen C.; Breitbart, Eckhard W.; Breuninger, Helmut; Diepgen, Thomas; Dirschka, Thomas; et al. (Journal der Deutschen Dermatologischen Gesellschaft, 2023)
CRIS-Team Scopus Importer:2023-10-27

S3-Leitlinie: Durchführung des Epikutantests mit Kontaktallergenen und Arzneimitteln – Kurzfassung Teil 1 - Mahler, Vera; Nast, Alexander; Bauer, Andrea; Becker, Detlef; Brasch, Jochen; Breuer, Kristine; Dickel, Heinrich; Drexler, Hans; Elsner, Peter; Geier, Johannes; John, Swen Malte; Kreft, Burkhard; et al. (Journal der Deutschen Dermatologischen Gesellschaft, 2019)
CRIS-Team Scopus Importer:2019-10-29

S3-Leitlinie: Durchführung des Epikutantests mit Kontaktallergenen und Arzneimitteln - Kurzfassung Teil 2. - Mahler, Vera; Nast, Alexander; Bauer, Andrea; Becker, Detlef; Brasch, Jochen; Breuer, Kristine; Dickel, Heinrich; Drexler, Hans; Elsner, Peter; Geier, Johannes; John, Swen Malte; Kreft, Burkhard; et al. (Journal der Deutschen Dermatologischen Gesellschaft, 2019)
Zusammenfassung Der diagnostische Standard zum Nachweis einer bestehenden allergischen Kontaktdermatitis ist der Epikutantest. Die vorliegende Leitlinie richtet sich an Assistenz- und Facharzte der Dermatologie, Allergologie und Arzte weiterer Fachgruppen in Klinik und Praxis, die an der Indikationsstellung oder Durchfuhrung von Epikutantests bei Patienten mit Kontaktekzemen und weiteren Spattypallergien beteiligt sind, sowie Kooperationspartner der Arzteschaft (Fachberufe im Gesundheitswesen, Kostentrager). Die Leitlinie zur Durchfuhrung des Epikutantests mit Kontaktallergenen wurde auf der Basis einer systematischen Literatursuche zu definierten Schlusselfragen evidenzbasiert und im formellen Konsensusverfahren (S3) von Dermatologen unter Einbindung von Padiatern, Arbeitsmedizinern, Assistenzpersonal und Patientenvertretern erstellt. Bezuglich der methodischen und inhaltlichen Arbeit, auf denen die Empfehlungen basieren, wird auf Methodenbericht und Evidenztabellen verwiesen. Die Leitlinie stellt allgemeine Aspekte der Epikutantestung sowie medizinrechtliche Aspekte dar. Es werden Empfehlungen gegeben zur Indikationsstellung, Patientenaufklarung, Auswahl von Testsubstanzen und Kammersystemen, Expositionsort, -dauer und Ablesezeitpunkten, Interpretation von Testreaktionen, endogenen und exogenen Einflussfaktoren, Testung besonderer Personengruppen (Kinder, Schwangere, Immunsupprimierte) sowie Risiken und unerwunschten Nebenwirkungen bei der Durchfuhrung des Epikutantests mit Kontaktallergenen.
EVALuna2:280871

Safety and tolerability of a single infusion of autologous ex vivo expanded regulatory T cells in adults with ulcerative colitis (ER-TREG 01): protocol of a phase 1, open-label, fast-track dose-escalation clinical trial - Voskens, Caroline; Stoica, Diane; Roessner, Susanne; Vitali, Francesco; Zundler, Sebastian; Rosenberg, Marita; Wiesinger, Manuel; Wunder, Jutta; Siegmund, Britta; Schuler-Thurner, Beatrice; Schuler, Gerold; Berking, Carola; et al. (BMJ Open, 2021)
Introduction Accumulating evidence suggests that the adoptive transfer of ex vivo expanded regulatory T cells (Treg) may overcome colitogenic immune responses in patients with inflammatory bowel diseases. The objective of the ER-TREG 01 trial is to assess safety and tolerability of a single infusion of autologous ex vivo expanded Treg in adults with ulcerative colitis.
CRIS-Team WoS Importer:2021-12-24

Safety of topical interventions for the treatment of actinic keratosis - Koch, Elias; Wessely, Anja; Steeb, Theresa; Berking, Carola; Heppt, Markus (Expert Opinion on Drug Safety, 2021)
Introduction: Actinic keratosis (AK) are proliferations of atypical keratinocytes that may eventually progress to cutaneous squamous cell carcinoma. Therefore, AK requires consequent and early treatment. Areas covered: A variety of effective approaches is currently available for the clearance of AK. These interventions may be applied either in a lesion-directed or field-directed mode as AK can occur as single or multiple lesions. Field-directed approaches typically comprise topical drug-mediated interventions which aim at eliminating all visible lesions and also at clearing subclinical changes of the actinically damaged field. However, most treatment options are associated with local adverse events such as erythema, scaling, pain, and rarely with systemic symptoms. This expert review provides a comprehensive and up-to-date overview of the safety considerations of the commonly prescribed topical treatment agents cyclooxygenase inhibitors, 5-fluorouracil, imiquimod, ingenol mebutate, and photodynamic therapy. All these therapies have been proven efficient, yet they differ considerably regarding their safety profile. Expert opinion: In the future, safety concerns will relate to long-term and irreversible adverse drug events instead of application site reactions. In particular, the rate of treatment-associated non-melanoma skin cancers will increasingly come into focus and warrant investigation in postmarketing surveillance trials with a long-term follow-up.
CRIS-Team Scopus Importer:2021-08-06
Keywords: 5-fluorouracil; actinic keratosis; diclofenac; imiquimod; ingenol mebutate; photodynamic therapy

Sarcoidosis Under Dendritic Cell Vaccination Immunotherapy in Long-term Responding Patients with Metastatic Melanoma - Uslu, Ugur; Erdmann, Michael; Schliep, Stefan; Dörrie, Jan; Schaft, Niels; Schuler, Gerold; Schuler-Thurner, Beatrice (Anticancer Research, 2017)
Sarcoidosis, a chronic inflammatory disorder, results from increased immune responses. Its development can be triggered in patients under immunotherapy, as activation of the immune system in these patients is desired. Since 1997, 249 patients with metastasized cutaneous melanoma (stage III and IV, AJCC 2009) have been treated with dendritic cell (DC)-based vaccines at our hospital. Three out of these patients were diagnosed with sarcoidosis after or during long-term DC vaccination therapy (1.20%). Metastatic disease was initially suspected based on the radiographic manifestation of lung masses or bilateral hilar lymphadenopathy. Histological assessment, however, revealed the appropriate diagnosis. Interestingly, all three patients are long-term responders and have remained free of metastatic or progressive disease for over a period of at least 4 years. In summary, sarcoidosis can occur in patients with cancer who have benefited from DC-based therapeutic vaccination and thus, its development, even with substantial delay, may be associated with successful anticancer immunotherapy.
EVALuna2:34321

SARS-CoV-2 Transmission from Presymptomatic Meeting Attendee, Germany - Hijnen, Dirkjan; Marzano, Angelo Valerio; Eyerich, Kilian; Geurtsvankessel, Corine; Giménez-Arnau, Ana Maria; Joly, Pascal; Vestergaard, Christian; Sticherling, Michael; Schmidt, Enno (Emerging Infectious Diseases, 2020)
During a meeting in Munich, Germany, a presymptomatic attendee with severe acute respiratory syndrome coronavirus 2 infected at least 11 of 13 other participants. Although 5 participants had no or mild symptoms, 6 had typical coronavirus disease, without dyspnea. Our findings suggest hand shaking and face-to-face contact as possible modes of transmission.
CRIS-Team WoS Importer:2020-08-07

SARS-CoV-2 vaccination responses in untreated, conventionally treated and anticytokine-treated patients with immune-mediated inflammatory diseases - Simon, David; Tascilar, Koray; Fagni, Filippo; Krönke, Gerhard; Kleyer, Arnd; Meder, Christine; Meder, Christine; Atreya, Raja; Leppkes, Moritz; Kremer, Andreas E.; Pachowsky, Milena; Schuch, Florian; et al. (Annals of the Rheumatic Diseases, 2021)
Objectives: To better understand the factors that influence the humoral immune response to vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs). Methods: Patients and controls from a large COVID-19 study, with (1) no previous history of COVID-19, (2) negative baseline anti-SARS-CoV-2 IgG test and (3) SARS-CoV-2 vaccination at least 10 days before serum collection were measured for anti-SARS-CoV-2 IgG. Demographic, disease-specific and vaccination-specific data were recorded. Results: Vaccination responses from 84 patients with IMID and 182 controls were analysed. While all controls developed anti-SARS-CoV-2 IgG, five patients with IMID failed to develop a response (p=0.003). Moreover, 99.5% of controls but only 90.5% of patients with IMID developed neutralising antibody activity (p=0.0008). Overall responses were delayed and reduced in patients (mean (SD): 6.47 (3.14)) compared with controls (9.36 (1.85); p<0.001). Estimated marginal means (95% CI) adjusted for age, sex and time from first vaccination to sampling were 8.48 (8.12-8.85) for controls and 6.90 (6.45-7.35) for IMIDs. Significantly reduced vaccination responses pertained to untreated, conventionally and anticytokine treated patients with IMID. Conclusions: Immune responses against the SARS-CoV-2 are delayed and reduced in patients with IMID. This effect is based on the disease itself rather than concomitant treatment.
CRIS-Team Scopus Importer:2021-05-21
Keywords: biological therapy; COVID-19; epidemiology; vaccination

Schlusswort - Heinzerling, Lucie (Deutsches Ärzteblatt international, 2019)
CRIS-Team Scopus Importer:2019-06-25

SCLE manifestation after mRNA COVID-19 vaccination - Rechtien, Laura; Erfurt-Berge, Cornelia; Sticherling, Michael (Journal of the European Academy of Dermatology and Venereology, 2022)
CRIS-Team WoS Importer:2022-01-14

Scurvy : A rare differential diagnosis of rheumatic diseases - Hofheinz, K.; Ganzleben, Ingo; Schliep, S.; Wacker, J.; Schett, Georg; Manger, Bernhard (Zeitschrift für Rheumatologie, 2016)
In December 2014 a patient presented to our clinic with the clinical symptoms of vasculitis. However, treatment with glucocorticoids did not lead to any improvement; therefore, the differential diagnostics were extended to other indications and ultimately led to the diagnosis of scurvy.This article describes the clinical picture of scurvy and its relationship to rheumatic diseases based on a clinical case and additional information from the literature. Differences and similarities with important rheumatological disease symptoms are presented.Scurvy is a rare hypovitaminosis disease which can be manifested in different forms. In addition to vasculitis the symptoms can also resemble arthritis and hemarthrosis is a typical finding. These symptoms can be accompanied by unspecific manifestations, such as muscle pain and due to impaired collagen synthesis characteristic features, such as corkscrew hair can be observed. The causal therapy of scurvy is substitution of ascorbic acid.Scurvy is a rare differential diagnosis in the context of rheumatic diseases. The indications for scurvy can be a lack of response to immunosuppressive and immunomodulatory drugs as well as individual symptoms, such as corkscrew hair.
EVALuna2:2047

Secondary prevention measures in anaphylaxis patients: Data from the anaphylaxis registry - Kraft, Magdalena; Knop, Macarena Pia; Renaudin, Jean-Marie; Scherer Hofmeier, Kathrin; Pfoehler, Claudia; Bilo, Maria Beatrice; Lang, Roland; Treudler, Regina; Wagner, Nicola; Spindler, Thomas; Hourihane, Jonathan O'B; Maris, Ioana; et al. (Allergy, 2019)
Background Patients with a history of anaphylaxis are at risk of future anaphylactic reactions. Thus, secondary prevention measures are recommended for these patients to prevent or attenuate the next reaction. Methods Data from the Anaphylaxis Registry were analyzed to identify secondary prevention measures offered to patients who experienced anaphylaxis. Our analysis included 7788 cases from 10 European countries and Brazil. Results The secondary prevention measures offered varied across the elicitors. A remarkable discrepancy was observed between prevention measures offered in specialized allergy centers (84% of patients were prescribed adrenaline autoinjectors following EAACI guidelines) and outside the centers: Here, EAACI guideline adherence was only 37%. In the multivariate analysis, the elicitor of the reaction, age of the patient, mastocytosis as comorbidity, severity of the reaction, and reimbursement/availability of the autoinjector influence physician's decision to prescribe one. Conclusions Based on the low implementation of guidelines concerning secondary prevention measures outside of specialized allergy centers, our findings highlight the importance of these specialized centers and the requirement of better education for primary healthcare and emergency physicians.
CRIS-Team WoS Importer:2019-11-01

Secondary resistance to sonidegib is rare in locally advanced basal cell carcinoma - Muñoz Couselo, Eva; Berking, Carola; Baurain, Jean François; Martelli, Serena; Arntz, Ramon; Savoia, Paola (Journal of the European Academy of Dermatology and Venereology, 2025)
CRIS-Team Scopus Importer:2025-03-28

Secondary syphilis infection under treatment with ustekinumab - Uslu, Ugur; Heppt, Franz; Sticherling, Michael (Clinical and Experimental Dermatology, 2017)
EVALuna2:34342

Second-line therapies for steroid-refractory immune-related adverse events in patients treated with immune checkpoint inhibitors - Ruf, Theresa; Kramer, Rafaela; Forschner, Andrea; Leiter, Ulrike; Meier, Friedegund; Reinhardt, Lydia; Dücker, Pia; Ertl, Carolin; Tomsitz, Dirk; Tietze, Julia K.; Gutzmer, Ralf; Dabrowski, Evelyn; et al. (European Journal of Cancer, 2024)
Background: Immune checkpoint inhibitors (ICI) induce adverse events (irAEs) that do not respond to steroids, i.e. steroid-refractory (sr) irAEs, and irAEs in which steroids cannot be tapered, i.e. steroid-dependent (sd) irAEs, in about 10% of cases. An evidence-based analysis of the effectiveness of second-line immunosuppressive agents with regard to irAE and tumor control is lacking. Methods: The international web-based Side Effect Registry Immuno-Oncology (SERIO; http://serio-registry.org) is a collaborative initiative with the Paul-Ehrlich-Institute to document rare, severe, complex or therapy-refractory immunotherapy-induced side effects. The registry was queried on August 1, 2023 for cases of irAEs which were treated with second-line therapies. Results: From a total of 1330 cases, 217 patients (16.3%) received 249 second‐line therapies. A total of 19 different second-line therapies were employed, including TNF-alpha antagonists (46.5%), intravenous immunoglobulins (IVIG; 19.1%), mycophenolate mofetil (15.9%), and methotrexate (3.6%). Therapy choices were determined by the type of irAE. The time to onset of sr-/sd-irAEs after ICI initiation did not consistently differ from steroid-responsive irAEs. While 74.3% of sr-/sd-irAEs resolved and 13.1% had improved, 4.3% persisted, 3.9% resulted in permanent sequelae, and 4.3% in death with ongoing symptoms. Infliximab exhibited potential for earlier symptom improvement compared to mycophenolate mofetil or IVIG. Tumor response in patients with second-line treated sd-/sr-irAE was similar to patients with irAEs treated with steroids only. Conclusion: Several second-line therapies are effective against sr-/sd-irAEs, the second-line therapies show no clear negative impact on tumor response, and infliximab shows potential for faster improvement of symptoms. However, prospective comparative data are needed.
CRIS-Team Scopus Importer:2024-05-03
Keywords: Immune checkpoint inhibitors; Immune-related adverse events; Second-line immunosuppressants; Steroid-dependent; Steroid-refractory

Secukinumab 2-weekly vs. 4-weekly dosing in patients with plaque-type psoriasis: results from the randomized GAIN study - Reich, K.; Koerber, A.; Mrowietz, U.; Sticherling, Michael; Sieder, C.; Frueh, J.; Bachhuber, T. (British Journal of Dermatology, 2020)
Background: Secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin-17A and shows long-lasting efficacy and safety in plaque psoriasis. More evidence is required to optimize secukinumab dosing according to clinical response. Objectives: GAIN compared the efficacy and safety of secukinumab 300 mg every 2 weeks (q2w) with 300 mg every 4 weeks (q4w) in patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) but not PASI 90 after 16 weeks. Methods: In total, 772 patients with moderate-to-severe plaque psoriasis received secukinumab 300 mg subcutaneously at baseline and weeks 1, 2, 3 and 4, then q4w until week 16. At week 16, patients with PASI ≥ 75 to PASI < 90 were randomized 1: 1 to continue q4w dosing (n = 162) or switch to q2w (n = 163) to week 32. The primary endpoint was superiority of q2w to q4w dosing for PASI 90 response at week 32. Results: PASI 90 response at week 32 was numerically greater with secukinumab 300 mg q2w than with secukinumab 300 mg q4w in suboptimal responders, but this did not reach statistical significance (64·4% vs. 57·4%; odds ratio 0·64, 95% confidence interval 0·39–1·07; P = 0·087). Although the primary endpoint was not met, absolute PASI was significantly lower at week 32 in q2w vs. q4w patients (2·11 vs. 2·84, P = 0·024). Significantly more patients with q2w vs. q4w dosing showed minimal disease activity (Investigator’s Global Assessment score 0 or 1: 73·0% vs. 64·1%, P < 0·05) and improved quality of life (Dermatology Life Quality Index score 0 or 1: 58·9% vs. 50·6%, P < 0·05) at week 32. No new or unexpected safety signals arose. Conclusions: Most patients achieved PASI 90 response with secukinumab q4w. There was potential benefit of q2w dosing in some suboptimal responders. Continued q4w treatment can improve response even after 16 weeks.
CRIS-Team Scopus Importer:2020-12-04

Secukinumab in adult patients with lichen planus: efficacy and safety results from the randomized placebo-controlled proof-of-concept PRELUDE study. - Passeron, Thierry; Reinhardt, Maximilian; Ehst, Benjamin; Weiss, Jonathan; Sluzevich, Jason; Sticherling, Michael; Reygagne, Pascal; Wohlrab, Johannes; Hertl, Michael; Fazel, Nasim; Muscianisi, Elisa; Fan, Heng; et al. (British Journal of Dermatology, 2024)
BACKGROUND: Patients with lichen planus (LP) refractory to available therapies often experience a high disease burden, representing a population with a clear unmet need for new treatments. OBJECTIVES: To evaluate the efficacy and safety of secukinumab 300 mg over 32 weeks in adult patients with biopsy-proven cutaneous LP (CLP), mucosal LP (MLP) or lichen planopilaris (LPP) that is inadequately controlled by topical corticosteroids. METHODS: PRELUDE was a randomized double-blind placebo-controlled phase II proof-of-concept study that enrolled patients with CLP, MLP or LPP. Eligible patients were randomized to either secukinumab 300 mg every 4 weeks for 32 weeks (SECQ4W) or placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks (SECQ2W) for 16 weeks. The primary endpoint was achievement of the newly designed Investigator's Global Assessment (IGA) score ≤ 2 at week 16. RESULTS: Overall, 111 patients were randomized (n = 37 each) to CLP, MLP and LPP cohorts. As the proof-of-concept criteria were not met for any of the three cohorts, the primary objective was not met. A numerically higher proportion of patients achieved IGA ≤ 2 response at week 16 with SECQ4W vs. placebo in the MLP 37.5% [95% credibility interval (Crl) 20.3-57.2] vs. 23.1% (95% Crl 6.5-49.2) and LPP cohorts [37.5% (95% Crl 20.2-57.3) vs. 30.8% (95% Crl 10.8-57.6)]. In the LPP cohort, a sustained response for IGA ≤ 2 from week 16 to week 32 was achieved with SECQ4W (week 16, 37.5%; week 32, 45.8%), and a substantial improvement was observed in IGA ≤ 2 response in patients from this cohort who switched from placebo (week 16, 30.8%) to SECQ2W after week 16 (week 32, 63.6%). The safety profile was consistent with the known profile of secukinumab and showed no new or unexpected signals. CONCLUSIONS: PRELUDE is the first randomized controlled basket trial evaluating interleukin (IL)-17A inhibition with secukinumab across three subtypes of LP. Secukinumab was well tolerated and safe, showing different response rates across the three subtypes, with numerical IGA improvements in MLP and LPP, and no response in CLP. The study raises the question of a differential role of IL-17A across LP subtypes. The novel IGA score showed significant correlation with both patient- and physician-reported outcome measurements.
EVALuna2:569075

Secukinumab in Pediatric Patients with Plaque Psoriasis: Pooled Safety Analysis from Two Phase 3 Randomized Clinical Trials - Sticherling, Michael; Nikkels, Arjen F.; Hamza, Ashraf M.; Kwong, Pearl; Szepietowski, Jacek C.; El Sayed, Mahira; Ghislain, Pierre Dominique; Khotko, Alkes A.; Patekar, Manmath; Ortmann, Christine Elke; Forrer, Pascal; Papanastasiou, Philemon; et al. (American Journal of Clinical Dermatology, 2023)
Background: Plaque psoriasis affects 1% of the pediatric population, negatively impacting quality of life. The efficacy and safety of secukinumab in pediatric patients with moderate to severe or severe chronic plaque psoriasis have been established in two pivotal phase 3 trials (open-label, NCT03668613; double-blind, NCT02471144). Objectives: The aims were to report the pooled safety of secukinumab up to 52 weeks from two studies in subgroups of pediatric patients stratified by age and bodyweight, and to present, alongside the pediatric data, the pooled safety data from four pivotal adult secukinumab trials. Methods: The safety of secukinumab was evaluated in subgroups of pediatric patients defined by age (6 to < 12 and 12 to < 18 years) and bodyweight (< 25 kg, 25 to < 50 kg, and ≥ 50 kg) in the pooled population. Patients received secukinumab low dose (LD; 75/75/150 mg), secukinumab high dose (HD; 75/150/300 mg), placebo, or etanercept (0.8 mg/kg). For safety analyses, data were pooled from the pediatric studies NCT03668613 and NCT02471144, and presented alongside the pooled data from four adult pivotal studies (NCT01365455, NCT01636687, NCT01358578, NCT01555125). Results: A total of 198 pediatric patients (overall exposure: 184.6 patient-years [PY]) and 1989 adult patients (1749.5 PY) receiving secukinumab up to week 52 were included in this analysis. At week 52, the incidence of adverse events (AEs) was lower in the lower age and bodyweight subgroups. The AEs reported within these subgroups were consistent with the overall AEs reported in this analysis. Overall, exposure-adjusted incidence rates for treatment-emergent AEs were lower in the secukinumab-treated pediatric pool (198.8/100 PY) compared with the etanercept (266.3/100 PY) and adult pools (256.1/100 PY). Up to 52 weeks, the incidence rates of the AEs in the secukinumab-treated patients in the 6 to < 12 years subgroup and 12 to < 18 years subgroup were 167.7/100 PY and 214.7/100 PY, respectively. Similarly, incidence rates of the AEs in the secukinumab-treated patients in the < 25 kg, 25 kg to < 50 kg, and ≥ 50 kg subgroups were 177.3/100 PY, 192.5/100 PY, and 206.8/100 PY, respectively. Nasopharyngitis was the most frequently reported AE in secukinumab-treated pediatric patients across age (< 12 years: 11.8/100 PY; ≥ 12 years: 42.4/100 PY) and bodyweight (< 25 kg: 22.8/100 PY; 25 kg to < 50 kg: 19.0/100 PY; ≥ 50 kg: 43.0/100 PY). Of the 198 secukinumab-treated pediatric patients, one reported nail Candida, one reported skin Candida, and two reported vulvovaginal Candida. Transient and mostly mild events of neutropenia were observed with secukinumab, none leading to study treatment discontinuation. No incidence of treatment-emergent anti-drug antibodies was reported in pediatric patients treated with secukinumab. Conclusions: Secukinumab was well tolerated in pediatric patients with moderate to severe and severe plaque psoriasis across age and bodyweight subgroups. The overall safety profile of secukinumab in pediatric patients was consistent with that of adult patients. ClinicalTrials.gov Identifier: NCT03668613 (Novartis Study Code CAIN457A2311, referred to as A2311), actual study start date: August 29, 2018; actual primary completion date: September 19, 2019; estimated study completion date: September 14, 2023. NCT02471144 (Novartis Study Code CAIN457A2310, referred to as A2310), study start date: September 29, 2015; primary completion date: December 13, 2018; estimated study completion date: March 31, 2023.
CRIS-Team Scopus Importer:2023-07-07

Secukinumab is superior to Fumaric Acid Esters in the Treatment of Patients with moderate to severe Plaque Psoriasis without previous Systemic Therapy for Improvement of Skin Symptoms: PASI and IGA mod. 2011-Results of the PRIME Study - Reich, K.; Mrowietz, U.; Augustin, M.; Thaci, D.; Kneidl, J.; Hentschke, C.; Simang, M.; Sieder, C.; Melzer, N.; Sticherling, Michael (2017)
EVALuna2:34358

Secukinumab is superior to Fumaric Acid Esters in the Treatment of Patients with moderate to severe Plaque Psoriasis without prior System Therapy with regard to compatibility-related Therapeutic Adherence: Safety Results of the PRIME Study - Mrowietz, U.; Augustin, M.; Thaci, D.; Reich, K.; Kneidl, J.; Hentschke, C.; Simang, M.; Sieder, C.; Melzer, N.; Sticherling, Michael (2017)
EVALuna2:34361

Secukinumab is superior to Fumaric Acid Esters in the Treatment of Patients with moderate to severe Plaque Psoriasis without prior System Therapy with respect to the Improvement of quality of life: DLQI and SF-36 Results of the PRIME Study - Augustin, M.; Thaci, D.; Reich, K.; Mrowietz, U.; Kneidl, J.; Hentschke, C.; Simang, M.; Sieder, C.; Melzer, N.; Sticherling, Michael (2017)
EVALuna2:34359

Secukinumab is superior to Fumaric Acid Esters in the Treatment of Patients with moderate to severe Plaque Psoriasis with without previous Systemic Therapy for Improvement of Nail Symptoms: NAPSI Results PRIME Study - Thaci, D.; Reich, K.; Mrowietz, U.; Augustin, M.; Kneidl, J.; Hentschke, C.; Simang, M.; Sieder, C.; Melzer, N.; Sticherling, Michael (2017)
EVALuna2:34360

Secukinumab is superior to fumaric acid esters in treating patients with moderate-to-severe plaque psoriasis who are naive to systemic treatments: results from the randomized controlled PRIME trial - Sticherling, Michael; Mrowietz, U.; Augustin, M.; Thaci, D.; Melzer, N.; Hentschke, C.; Kneidl, J.; Sieder, C.; Reich, K. (British Journal of Dermatology, 2017)
BACKGROUND: Secukinumab is a fully human antibody that neutralizes interleukin-17A. It has significant efficacy and a favourable safety profile in moderate-to-severe plaque psoriasis and psoriatic arthritis. OBJECTIVES: To compare secukinumab with fumaric acid esters (FAEs) in a randomized controlled trial. METHODS: In this 24-week, randomized, open-label, multicentre study with blinded assessment, patients with moderate-to-severe plaque psoriasis, naive to systemic treatments, were randomized to receive secukinumab 300 mg subcutaneously or oral FAEs. The primary end point was ≥ 75% improvement from baseline Psoriasis Area and Severity Index score (PASI 75 response) at week 24, and missing patients were considered responders if they were responders at the time of dropout. RESULTS: In total 202 patients were randomized and 200 were treated with at least one dose. Outcomes at week 24 were available for 147 and imputed for 53 patients. Discontinuations were mostly due to adverse events, which occurred more frequently in the FAE group (1·9% vs. 33·0%). At week 24, significantly more patients receiving secukinumab compared with FAEs achieved PASI 75 response (89·5% vs. 33·7%, P < 0·001), PASI 90 response (81·0% vs. 28·4%, P < 0·001) and Dermatology Life Quality Index 0 or 1 response (71·4% vs. 25·3%, P < 0·001). CONCLUSIONS: Secukinumab demonstrated superior efficacy to FAEs in patients with psoriasis over a 24-week period.
EVALuna2:34340

Secukinumab leads to shifts from stage-based towards response-based disease clusters-comparative data from very early and established psoriatic arthritis - Kampylafka, Eleni; Tascilar, Koray; Lerchen, Veronika; Linz, Christina; Sokolova, Maria; Zekovic, Ana; Kleyer, Arnd; Simon, David; Rech, Jürgen; Sticherling, Michael; Schett, Georg; Hueber, Axel (Arthritis Research & Therapy, 2020)
Background: Limited information exists about the very early forms of psoriatic arthritis. In particular, differences and responsiveness of patient-reported outcomes (PROs) in very early as compared to established PsA have not been investigated to date. Methods: Cross-sectional and prospective longitudinal evaluation of PROs related to pain (VAS), physical function (HAQ-DI, SF-36 physical), mental function (SF-36 mental), impact of psoriatic skin (DLQI), joint (PsAID), and global disease (VAS) in two small prospective observational studies on secukinumab 300 mg over 6 months in very early disease patients (IVEPSA study, N = 20) and established PsA (PSARTROS study, N = 20). Cluster analysis was performed at baseline and 24-weeks of follow-up. Results: While responses in pain and physical activity-related PROs to secukinumab were more pronounced in established PsA than a very early disease, effects on PROs related to general health perception, as well as those related to emotional and mental well-being, were modified in a similar way in very early disease and established PsA. Cluster analysis based on global disease activity and PROs showed that baseline clusters reflected very early disease and established PsA, while after secukinumab treatment these clusters were abolished and new clusters based on differential responses to physically and mentally oriented PROs formed. Conclusions: Inhibition of IL-17A by secukinumab leads to comprehensive improvement of general health perception and mental well-being in very early and established PsA, while overall responses in pain and physical activity are more pronounced in established disease. Most importantly, treatment restructures the original patients' clusters based on disease stage and leads to the formation of new clusters that reflect their response in physical and mental-orientated PROs. Trial registration: NCT02483234, registered 26 June 2015, retrospectively registered.
CRIS-Team Scopus Importer:2020-10-02
Keywords: Cluster analysis; IL-17A; Psoriatic arthritis; Quality of life; Secukinumab

Secukinumab Treatment of moderate to severe Plaque Psoriasis in the clinical Routine Care: Baseline Data from the PROSPECT Study on Psoriasis Pre-treatment - Von Kiedrowski, R.; Korber, A.; Kraehn-Senftleben, G.; Sticherling, Michael; Lange, L.; Bachhuber, T.; Kasparek, T. R.; Augustin, M.; Thaci, D.; Amon, U. (2017)
EVALuna2:34357

Select Clr-g Expression on Activated Dendritic Cells Facilitates Cognate Interaction with a Minor Subset of Splenic NK Cells Expressing the Inhibitory Nkrp1g Receptor - Friede, Miriam E.; Leibelt, Stefan; Dudziak, Diana; Steinle, Alexander (Journal of Immunology, 2018)
Natural killer gene complex-encoded immunomodulatory C-type lectin-like receptors include members of the NKRP1 and C-type lectin-like 2 (CLEC2) gene families, which constitute genetically linked receptor-ligand pairs and are thought to allow for NK cell-mediated immunosurveillance of stressed or infected tissues. The mouse C-type lectin-like receptor Nkrp1g was previously shown to form several receptor-ligand pairs with the CLEC2 proteins Clr-d, Clr-f, and Clr-g, respectively. However, the physiological expression of Nkrp1g and its CLEC2 ligands as well as their functional relevance remained poorly understood. Recently, we demonstrated a gut-restricted expression of Clr-f on intestinal epithelial cells that is spatially matched by Nkrp1g on subsets of intraepithelial lymphocytes. In this study, we investigated expression and ligand interaction of Nkrp1g in the splenic compartment, and found an exclusive expression on a small subset of NK cells that upregulates Nkrp1g after cytokine exposure. Whereas transcripts of Clr-d and Clr-f are virtually absent from the spleen, Clr-g transcripts were abundantly detected throughout different leukocyte populations and hematopoietic cell lines. However, a newly generated anti-Clr-g mAb detected only residual Clr-g surface expression on splenic monocytes, whereas many hematopoietic cell lines brightly display Clr-g. Clr-g surface expression was strongly upregulated on splenic CD8α+ conventional dendritic cells (DCs) and plasmacytoid DCs upon TLR-mediated activation and detectable by Nkrp1g, which dampens NK cell effector functions upon Clr-g engagement. Hence, different to the intestinal tract, in the spleen, Nkrp1g is selectively expressed by a subset of NK cells, thereby potentially allowing for an inhibitory engagement with Clr-g-expressing activated DCs during immune responses.
EVALuna2:34802

Select hyperactivating NLRP3 ligands enhance the TH1-and TH17-inducing potential of human type 2 conventional dendritic cells - Hatscher, Lukas; Lehmann, Christian; Purbojo, Ariawan; Onderka, Constantin; Liang, Chunguang; Hartmann, Arndt; Cesnjevar, Robert; Bruns, Heiko; Gross, Olaf; Nimmerjahn, Falk; Burmazovic, Ivana Ivanovic; Kunz, Meik; et al. (Science Signaling, 2021)
The detection of microorganisms and danger signals by pattern recognition receptors on dendritic cells (DCs) and the consequent formation of inflammasomes are pivotal for initiating protective immune responses. Although the activation of inflammasomes leading to secretion of the cytokine IL-1 is typically accompanied by pyroptosis (an inflammatory form of lytic programmed cell death), some cells can survive and exist in a state of hyperactivation. Here, we found that the conventional type 2 DC (cDC2) subset is the major human DC subset that is transcriptionally and functionally poised for inflammasome formation and response without pyroptosis. When cDC2 were stimulated with ligands that relatively weakly activated the inflammasome, the cells did not enter pyroptosis but instead secreted IL-12 family cytokines and IL-1. These cytokines induced prominent T helper type 1 (TH1) and TH17 responses that were superior to those seen in response to Toll-like receptor (TLR) stimulation alone or to stronger, classical inflammasome ligands. These findings not only define the human cDC2 subpopulation as a prime target for the treatment of inflammasome-dependent inflammatory diseases but may also inform new approaches for adjuvant and vaccine development.
CRIS-Team Scopus Importer:2021-05-14
Keywords: Dendritic cells; cDC2; CD1c; inflammasome; hyperactivation; L18-MDP; T cell differentiation

Select hyperactivating NLRP3 ligands enhance the TH1-and TH17-inducing potential of human type 2 conventional dendritic cells - Heger, Lukas; Hatscher, Lukas; Lehmann, Christian; Purbojo, Ariawan; Onderka, Constantin; Liang, C.; Hartmann, Arndt; Cesnjevar, Robert; Bruns, Heiko; Gross, O.; Nimmerjahn, Falk; Ivanovic-Burmazovic, I.; et al. (EXPERIMENTAL DERMATOLOGY, 2022)
CRIS-Team WoS Importer:2022-03-04

Selection of adenovirus-specific and Epstein-Barr virus-specific T cells with major histocompatibility class I streptamers under Good Manufacturing Practice (GMP)-compliant conditions - Freimueller, Christine; Stemberger, Julia; Artwohl, Michaela; Germeroth, Lothar; Witt, Volker; Fischer, Gottfried; Tischer, Sabine; Eiz-Vesper, Britta; Knippertz, Ilka; Dörrie, Jan; Schaft, Niels; Lion, Thomas; et al. (Cytotherapy, 2015)
Despite antiviral drug therapies, human adenovirus (HAdV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections still contribute substantially to transplant-related death of patients after hematopoietic stem cell transplantation. Earlier clinical studies demonstrated successful adoptive transfer of magnetically selected CMV-specific T cells via removable, and thus Good Manufacturing Practice-compliant, major histocompatibility class I streptamers. Thus, the primary focus of the present study was the selection of HAdV-streptamer+ T cells, although in three experiments, EBV-streptamer+ T cells were also selected.Cells from leukaphereses of healthy donors were prepared in large (1-6 × 10(9)) and small (25 × 10(6)) cell batches. Whereas the larger batch was directly labeled with streptamers to select HAdV- and/or EBV-specific T cells (large-scale), the smaller batch was used to generate in vitro virus-specific T-cell lines before streptamer labeling for streptamer selection (small-scale). Isolation of HAdV- and/or EBV-specific T cells was performed with the use of the CliniMACS device.The purity of HAdV- and EBV-streptamer+ T cells among CD3+ cells, obtained from large-scale selection, was up to 6.7% and 44%, respectively. If HAdV- and EBV-streptamers were applied simultaneously, the purity of antigen-specific T cells reached up to 50.7%. A further increase in purity reaching up to 98% was achieved by small-scale selection of HAdV-specific T cells. All final products fulfilled the microbiological and chemical release criteria. Interferon-?-response indicating functional activity was seen in 6 of 9 HAdV and 2 of 3 EBV large-scale selections and in 2 of 3 HAdV small-scale selections.HAdV-streptamers were shown to be clinically feasible for few patients after the large-scale approach but for larger patient numbers if combined with EBV-streptamers or after the small-scale approach.
EVALuna2:19523

Semi-Automatic Cell Correspondence Analysis Using Iterative Point Cloud Registration - Chen, Shuqing; Gehrer, Simone; Kaliman, Sara; Ravikumar, Nishant; Becit, Abdurrahman; Aliee, Maryam; Dudziak, Diana; Merkel, Rudolf; Smith, Ana-Suncana; Maier, Andreas (Bildverarbeitung für die Medizin 2019. Informatik aktuell., 2019)

Senescence markers: Predictive for response to checkpoint inhibitors - Moreira, Alvaro; Gross, Stefanie; Kirchberger, Michael Constantin; Erdmann, Michael; Schuler, Gerold; Heinzerling, Lucie (International Journal of Cancer, 2019)
Recent studies suggest that the age-related remodeling of the immune system, known as immunosenescence, could impact the efficacy of immune checkpoint inhibitors in leukemia or nonsmall cell lung cancer. We investigated whether senescence markers can predict response to checkpoint inhibitor therapy in melanoma patients. The peripheral blood of patients with newly diagnosed, untreated metastatic melanoma was analyzed by flow cytometry to correlate the frequency of senescence markers with clinical response as measured by RECIST after 12 weeks of treatment with immune checkpoint inhibitors. The loss of surface markers CD27 and CD28 or the expression of Tim-3 and CD57 on T cells was associated with resistance to checkpoint inhibitor blockade, presenting these phenotypes as possible predictive biomarkers for checkpoint inhibitor therapy. Immunosenescence seems to impact on the response to checkpoint inhibitor therapy in melanoma patients. Thus, lymphocyte phenotyping for senescence markers, with the introduction of immunosenescence panels, could be predictive for checkpoint inhibitor response.
CRIS-Team Scopus Importer:2019-05-21
Keywords: biomarker; immune checkpoint inhibitors; immunosenescence; melanoma

Sensitive allele-specific real-time PCR test for mutations in BRAF codon V600 in skin melanoma - Pisareva, Ekaterina; Gutkina, Nadezhda; Kovalenko, Sergei; Kuehnapfel, Sarah; Hartmann, Arndt; Heinzerling, Lucie; Schneider-Stock, Regine; Lyubchenko, Lyudmila; Shamanin, Vladimir A. (Melanoma Research, 2014)
Mutations at BRAF codon V600 are used as predictive biomarkers for targeted therapy of skin melanoma. Here, a simple sensitive test to detect mutations of BRAF-V600 was developed using real-time PCR with allele-specific primers and TaqMan probes. Two versions of the test using sense and antisense allele-specific primers were designed and evaluated. The test detected 1% mutant allele V600E/K in 10 ng DNA standard made from wild-type human DNA spiked with BRAF-V600E or the V600K plasmid. The test was validated on clinical formalin-fixed paraffin-embedded samples of skin melanoma using pyrosequencing as a reference method. In the clinical samples, we detected the common mutation V600E, as well as the rare mutations V600K, V600E2 (codon GAA), V600E2 K601del, V600D-K601del, and V600R. In comparison with pyrosequencing, both versions of the test had 100% specificity with sensitivities of 97 and 86% for sense and antisense allele-specific primers, respectively. Using the PCR test with sense allele-specific primers, mutations in V600 were found in 33 of 51 Russian patients (64.7%) with cutaneous melanoma. This closed-tube real-time PCR test can be used as a simple and sensitive assay for mutations of BRAF-V600 in cutaneous melanoma.
EVALuna2:6621

Sensitivity and specificity of standardised allergen extracts in skin prick test for diagnoses of IgE-mediated respiratory allergies - Wagner, Nicola; Rudert, Michael (Clinical and Translational Allergy, 2019)
Background: Skin prick tests (SPTs) are essential for the diagnosis of IgE-mediated allergy and are influenced by extract quality, biological potency and concentration of allergen.
CRIS-Team WoS Importer:2019-03-26

Sentinel Lymph Node Dissection in Head and Neck Melanoma has Prognostic Impact on Disease-Free and Overall Survival - Leiter, Ulrike; Eigentler, Thomas K.; Haefner, Hans-Martin; Krimmel, Michael; Uslu, Ugur; Keim, Ulrike; Weide, Benjamin; Breuninger, Helmut; Martus, Peter; Garbe, Claus (Annals of Surgical Oncology, 2015)
Sentinel lymph node biopsy (SLNB) plays an important role in the prognostic classification of melanoma and is now a standard staging procedure. However, due to the complex drainage pattern and the risk of site associated morbidity, the potential survival benefit of SLNB is controversial in head and neck (H&N) melanoma.Patients with primary H&N melanoma with a tumor thickness >=1.00 mm diagnosed in the Department of Dermatology, University of Tuebingen, Germany between 1991 and 2010 were included in this study. Regarding patterns of metastases, disease-free, and overall-survival, 259 patients with SLNB were compared retrospectively to 218 patients without SLNB.The detection of micrometastasis in SLN proved to be a significant prognostic factor in H&N patients [hazard ratio (HR) 3.69, p < 0.0001]. A significant improvement of recurrence-free survival (RFS, p = 0.011), regional lymph node metastasis-free survival (LFS, p = 0.007), and distant metastasis-free survival (DMSF, p = 0.015) was observed for patients with SLNB versus non-SLNB. Furthermore, a trend towards better overall survival (OS) was found (p = 0.053) for the SLNB group.SLNB improved prognostic outcome in H&N melanoma in terms of disease-free and distant metastases survival, reduced subsequent regional lymph node metastases, and showed a trend towards a better OS.
EVALuna2:19555

Sepsis and Autoimmune Disease: Pathology, Systems Medicine, and Artificial Intelligence - Jendrek, Sebastian; Lai, Xin; Riemekasten, Gabriela; Vera González, Julio; Schmeck, Bernd; Bertrams, Wilhelm (Systems Medicine: Integrative, Qualitative and Computational Approaches, 2020)
Pathologic conditions in which the body׳s own response to an insult is the most damaging aspect of the disease, such as in auto-immunity and sepsis, have seen researchers and clinicians struggle to find therapeutic targets for decades. Large clinical cohorts and advanced molecular biology are key elements in the search for new medications. Methodology with increasing resolution is constantly being developed to identify new subsets of cells embedded in the disease framework and to map their complex gene expression profile, secretome and epigenome. Big data that is thus being generated require advanced computational methods in order to distil knowledge from them, and in order to use them as the basis for modeling approaches. Models need to integrate the spatial, temporal and organizational domains in order to reflect biology with a certain degree of fidelity. The ultimate goal of the combined efforts of clinical studies, molecular biology with cutting-edge technology and comprehensive mathematical modeling is the bench-to-bedside translation of knowledge to reduce the socio-economic burden of disease.
CRIS-Team Scopus Importer:2024-12-16
Keywords: Agent-based model (ABM); Autoantibodies; Autoimmunity; Biomarkers in rheumatic diseases; Cytokine; Epigenetics in rheumatic diseases; Genome-wide association study (GWAS); Mathematical modeling; Micro-thrombosis; Network analysis; systems level analysis; Ordinary differential equation (ODE); Organ dysfunction; Sepsis; Septic shock; Transcriptome analysis

Sequence-dependent cross-resistance of combined radiotherapy plus BRAF(V600E) inhibition in melanoma - Shannan, B.; Matschke, J.; Chauvistre, H.; Vogel, F.; Klein, D.; Meier, F.; Westphal, D.; Bruns, J.; Rauschenberg, R.; Utikal, J.; Forschner, A.; Berking, C.; et al. (European Journal of Cancer, 2019)
Introduction: Treatment of patients with metastatic melanoma is hampered by drug-resistance and often requires combination with radiotherapy as last-resort option. However, also after radiotherapy, clinical relapses are common. Methods & results: Our preclinical models indicated a higher rate of tumour relapse when melanoma cells were first treated with BRAF V600E inhibition (BRAFi) followed by radiotherapy as compared to the reverse sequence. Accordingly, retrospective follow-up data from 65 stage-IV melanoma patients with irradiated melanoma brain metastases confirmed a shortened duration of local response of mitogen-activated protein kinase (MAPK)-inhibitor–pretreated compared with MAPK-inhibitor–naïve intracranial metastases. On the molecular level, we identified JARID1B/KDM5B as a cellular marker for cross-resistance between BRAFi and radiotherapy. JARID1B high cells appeared more frequently under upfront BRAFi as compared with upfront radiation. JARID1B favours cell survival by transcriptional regulation of genes controlling cell cycle, DNA repair and cell death. Conclusion: The level of cross-resistance between combined MAPK inhibition and radiotherapy is dependent on the treatment sequence. JARID1B may represent a novel therapy-overarching resistance marker.
CRIS-Team WoS Importer:2019-03-06
Keywords: Cross-resistance; JARID1B/KDM5B; Melanoma; Radiotherapy; Repopulation; Resistance; Slow-cycling cells; Targeted therapy; Therapy sequencing

Sequence-function analysis of three T cell receptors targeting the HIV-1 p17 - Mummert, Christiane; Hofmann, Christian; Hueckelhoven, Angela G.; Bergmann, Silke; Müller-Schmucker, Sandra; Harrer, Ellen G.; Dörrie, Jan; Schaft, Niels; Harrer, Thomas (2016)
EVALuna2:19635

Serial or Parallel Metastasis of Cutaneous Melanoma? A Study of the German Central Malignant Melanoma Registry - Gassenmaier, Maximilian; Eigentler, Thomas Kurt; Keim, Ulrike; Goebeler, Matthias; Fiedler, Eckhard; Schuler, Gerold; Leiter, Ulrike; Weide, Benjamin; Grischke, Eva-Maria; Martus, Peter; Garbe, Claus (Journal of Investigative Dermatology, 2017)
For more than a century the Halstedian hypothesis of contiguous metastasis from the primary tumor through the lymphatics to distant sites shaped lymph node surgery for melanoma. We challenge this dogma of serial metastatic dissemination. A single-center series of 2,299 patients with cutaneous metastatic melanoma was investigated to analyze overall survival and distant metastasis-free survival of stage IV patients with or without primary lymphatic metastasis. Results were then compared with those of 2,134 patients from three independent centers of the German Central Malignant Melanoma Registry. A multivariate binary logistic regression model was used to identify risk factors for the initial metastatic pathway. Distant metastasis-free survival (hazard ratio = 1.02; 95% confidence interval = 0.91-1.14; P = 0.76) and overall survival (HR = 1.09; 95% CI = 0.96-1.23; P = 0.177) did not differ between stage IV patients with primary hematogenous or primary lymphatic metastasis. Melanoma localization was the only significant risk factor for the initial metastatic pathway. These findings indicate that regional and distant metastases originate from the primary tumor itself in a rather parallel than serial fashion and could explain the lack of survival benefit associated with immediate complete lymph node dissection in sentinel lymph node-positive melanoma patients.
EVALuna2:34312

SERIO - Side Effect Registry Immuno-Oncology Side Effect Registry for rare, severe and complex Side Effects of Immunotherapy - Kramer, Rafaela; Mentzer, D.; Erdmann, M.; Knauss, S.; Broeckelmann, P. J.; Hassel, J. C.; Ugurel, S.; Pavel, Marianne Ellen; Nickel, Franziska; Landendinger, M.; Fuchs, Friederike; Meidenbauer, Norbert; et al. (JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, 2020)
CRIS-Team WoS Importer:2020-09-11

Serio - Side Effect Registry in Immuno-Oncology - Koutzamanidis, Rafaela; Mentzer, Dirk; Knauss, Samuel; Broeckelmann, Paul J.; Hassel, Jessica Cecile; Ugurel-Becker, Selma; Pavel, Marianne Ellen; Nickel, Florian; Landendinger, Melanie; Fuchs, Florian; Meidenbauer, Norbert; Jefremow, Andre; et al. (ONCOLOGY RESEARCH AND TREATMENT, 2020)
CRIS-Team WoS Importer:2020-03-20

Serositis in Association with System Therapy with Checkpoint Inhibitors - More frequent than thought? - An Evaluation of the SERIO Adverse Event Registry - Zierold, S.; Kramer, R.; Erdmann, Michael; Akcetin, S. L.; Maier, A. M.; Koenig, A.; Theurich, S.; French, L. E.; Heinzerling, Lucie (JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, 2021)
CRIS-Team WoS Importer:2021-09-24

Serum autoantibody reactivity in bullous pemphigoid is associated with neuropsychiatric disorders and the use of antidiabetics and antipsychotics: a large, prospective cohort study - Dikmen, H. O.; Yilmaz, K.; Benoit, S.; Bernard, P.; Drenovska, Kossara; Gerdes, S.; Glaeser, R.; Guenther, C.; Homey, B.; Horvath, O. N.; Huilaja, L.; Joly, P.; et al. (Journal of the European Academy of Dermatology and Venereology, 2022)
Background: Bullous pemphigoid (BP), the by far most frequent autoimmune blistering skin disease (AIBD), is immunopathologically characterized by autoantibodies against the two hemidesmosomal proteins BP180 (collagen type XVII) and BP230 (BPAG1 or dystonin). Several comorbidities and potentially disease-inducing medication have been described in BP, yet a systematic analysis of these clinically relevant findings and autoantibody reactivities has not been performed. Objective: To determine associations of autoantibody reactivities with comorbidities and concomitant medication. Methods: In this prospective multicenter study, 499 patients diagnosed with BP in 16 European referral centers were included. The relation between anti-BP180 NC16A and anti-BP230 IgG ELISA values at the time of diagnosis as well as comorbidities and concomitant medication collected by a standardized form were analysed. Results: An association between higher serum anti-BP180 reactivity and neuropsychiatric but not atopic and metabolic disorders was observed as well as with the use of insulin or antipsychotics but not with dipeptidyl peptidase-4 (DPP4) inhibitors, inhibitors of platelet aggregation and L-thyroxine. The use of DPP4 inhibitors was associated with less anti-BP180 and anti-BP230 reactivity compared with BP patients without these drugs. This finding was even more pronounced when compared with diabetic BP patients without DPP4 inhibitors. Associations between anti-BP180 and anti-BP230 reactivities were also found in patients using insulin and antipsychotics, respectively, compared with patients without this medication, but not for the use of inhibitors of platelet aggregation, and L-thyroxine. Conclusion: Taken together, these data imply a relation between autoantibody reactivities at the time of diagnosis and both neuropsychiatric comorbidities as well as distinct concomitant medication suggesting a link between the pathological immune mechanisms and clinical conditions that precede the clinically overt AIBD.
CRIS-Team Scopus Importer:2022-07-22

Serum extracellular matrix biomarkers in rheumatoid arthritis, psoriatic arthritis and psoriasis and their association with hand function - Port, Helena; Coppers, Birte; Tragl, Sonja; Manger, Eva; Niemiec, Lisa Maria; Bayat, Sara; Simon, David; Fagni, Filippo; Corte, Giulia; Bay-Jensen, Anne Christine; Tascilar, Koray; Hueber, Axel; et al. (Scientific Reports, 2025)
Inflammatory arthritis, including rheumatoid arthritis and psoriatic arthritis, is characterized by physical function impairment. This becomes apparent even before arthritis onset, as in psoriasis (PsO). Chronic inflammation triggers an accelerated remodeling of the extracellular matrix (ECM), resulting in released ECM fragments detectable in blood. We aimed to investigate levels of blood-based ECM biomarkers in patients with RA, PsA, PsO, and healthy controls and to explore the association of ECM biomarkers with hand function impairments. Patients with RA (n = 85), PsA (n = 115), PsO (n = 102) and controls (n = 110) were included in this cross-sectional study. ECM catabolic (C1M, C2M, C3M, C4M, PRO-C4, C6M, ARG), formation (PRO-C1, PRO-C3, PRO-C6) and inflammation biomarkers (VICM) were measured in serum from all patients. Objective hand function (fine motor skills (Moberg-Picking-Up Test), isometric grip strength (dynamometer) and patient-perceived hand function (Michigan Hand Questionnaire (MHQ)) were assessed. Patients with RA and PsA received treatment with disease-modifying anti-rheumatic drugs. VICM levels were higher in RA, PsA, and PsO than in controls (p < 0.0001). PsA and PsO showed higher C4M levels compared to controls (p < 0.0001, p < 0.0001), while C6M was lower in patients with RA, PsA and PsO than in controls (p < 0.0001, p < 0.001, p < 0.01). PsO presented with higher levels of C1M compared to controls and to RA (p < 0.001 and p < 0.0001). PRO-C6 correlated negatively with MHQ (ρ = -0.39, p < 0.01) and grip strength (ρ = -0.31, p < 0.05) in PsO, while only weak correlations were observed between biomarkers and hand function scores for RA and PsA patients (all ρ < ± 0.2–0.3). Patients with RA, PsA, and PsO showed significant alterations in ECM remodeling biomarkers. Especially PsA and PsO had higher levels of inflammatory biomarkers compared to RA and controls, likely due to modulation by treatment. Predominantly in PsO, ECM formation biomarkers were associated with hand function impairments.<br
Keywords: Extracellular matrix; Biochemical markers; Rheumatoid arthritis; Psoriatic arthritis; Psoriasis; Hand function

Serum interleukin-8 reflects tumor burden and treatment response across malignancies of multiple tissue origins - Sanmamed, Miguel F.; Carranza-Rua, Omar; Alfaro, Carlos; Onate, Carmen; Martin-Algarra, Salvador; Perez, Guiomar; Landazuri, Sara F.; Gonzalez, Alvaro; Gross, Stefanie; Rodriguez, Inmaculada; Munoz-Calleja, Cecilia; Rodriguez-Ruiz, Maria; et al. (Clinical Cancer Research, 2014)
Interleukin-8 (IL8) is a chemokine produced by malignant cells of multiple cancer types. It exerts various functions in shaping protumoral vascularization and inflammation/immunity. We evaluated sequential levels of serum IL8 in preclinical tumor models and in patients to assess its ability to estimate tumor burden.IL8 levels were monitored by sandwich ELISAs in cultured tumor cells supernatants, tumor-xenografted mice serum, and in samples from 126 patients with cancer. We correlated IL8 serum levels with baseline tumor burden and with treatment-induced changes in tumor burden, as well as with prognosis.IL8 concentrations correlated with the number of IL8-producing tumor cells in culture. In xenografted neoplasms, IL8 serum levels rapidly dropped after surgical excision, indicating an accurate correlation with tumor burden. In patients with melanoma (n = 16), renal cell carcinoma (RCC; n = 23), non-small cell lung cancer (NSCLC; n = 21), or hepatocellular carcinoma (HCC; n = 30), serum IL8 concentrations correlated with tumor burden and stage, survival (melanoma, n = 16; RCC, n = 23; HCC, n = 33), and objective responses to therapy, including those to BRAF inhibitors (melanoma, n = 16) and immunomodulatory monoclonal antibodies (melanoma, n = 8). IL8 concentrations in urine (n = 18) were mainly elevated in tumors with direct contact with the urinary tract.IL8 levels correlate with tumor burden in preclinical models and in patients with cancer. IL8 is a potentially useful biomarker to monitor changes in tumor burden following anticancer therapy, and has prognostic significance.
EVALuna2:19512

Serum levels of miR-320 family members are associated with clinical parameters and diagnosis in prostate cancer patients - Lieb, Verena; Weigelt, Katrin; Scheinost, Lena; Fischer, Kersten; Greither, Thomas; Marcou, Marios; Theil, Gerit; Klocker, Helmut; Holzhausen, Hans Juergen; Lai, Xin; Vera, Julio; Ekici, Arif Bülent; et al. (Oncotarget, 2018)
We studied the association of the serum levels of the microRNA family members miR-320a/-b/-c with clinico-pathological data to assess their applicability as diagnostic biomarker in prostate cancer (PCa) patients. The levels of miR-320a/-b/-c in 3 groups were evaluated by qRT-PCR (145 patients with PCa, 31 patients with benign prostatic hyperplasia (BPH) and 19 healthy controls). The levels of the three family members of miR-320 were directly correlated within each group (P < 0.001), but they differed significantly among the three groups (P < 0.001). The serum levels of the miR-320 family members were significantly increased in older patients compared to younger patients (≤ 66 years vs. > 66 years, P ≤ 0.001). In addition, the levels of all three miR-320 family members were significantly different in patients with low tumor stage compared with those with high tumor stage (miR-320a: P = 0.034; miR-320b: P = 0.006; miR-320c: P = 0.007) and in patients with low serum PSA compared with those with high serum PSA (≤ 4 ng vs. > 4 ng; miR-320a: P = 0.003; miR-320b: P = 0.003; miR-320c: P = 0.006). The levels of these miRNAs were inversely correlated with serum PSA levels. Detection in the serum samples of PCa patients with or without PSA relapse revealed higher levels of miR-320a/-b/-c in the group without PSA relapse before/after radical prostatectomy than in that with PCa relapse. In summary, the differences among the PCa/BPH/healthy control groups with respect to miR-320a/-b/-c levels in conjunction with higher levels in patients without a PSA relapse than in those with a relapse suggest the diagnostic potential of these miRNA-320 family members in PCa patients.
EVALuna2:35121

Severe bullous pemphigoid in a 4-month-old infant - Holtsche, Maike M.; van Beek, Nina; Vorobyev, Artem; Schmidt, Enno; Lauten, Melchior; Wagner, Nicola; Krickau, Tobias; Anemüller, Waltraud (Journal der Deutschen Dermatologischen Gesellschaft, 2024)
CRIS-Team Scopus Importer:2024-07-26

Short Peptide Vaccine Induces CD4+ T Helper Cells in Patients with Different Solid Cancers - Gross, Stefanie; Lennerz, Volker; Gallerani, Elisa; Mach, Nicolas; Boehm, Steffen; Hess, Dagmar; Von Boehmer, Lotta; Knuth, Alexander; Ochsenbein, Adrian; Gnad-Vogt, Ulrike; Forssmann, Ulf; Woelfel, Thomas; et al. (Cancer Immunology Research, 2016)
Previous cancer vaccination trials often aimed to activate CD8(+) cytotoxic T-cell (CTL) responses with short (8-10mer) peptides and targeted CD4(+) helper T cells (TH) with HLA class II-binding longer peptides (12-16 mer) that were derived from tumor antigens. Accordingly, a study of immunomonitoring focused on the detection of CTL responses to the short, and TH responses to the long, peptides. The possible induction of concurrent TH responses to short peptides was widely neglected. In a recent phase I vaccination trial, 53 patients with different solid cancers were vaccinated with EMD640744, a cocktail of five survivin-derived short (9- or 10-mer) peptides in Montanide ISA 51VG. We monitored 49 patients and found strong CD8(+) T-cell responses in 63% of the patients. In addition, we unexpectedly found CD4(+) TH cell responses against at least two of the five short peptides in 61% (23/38) of the patients analyzed. The two peptides were recognized by HLA-DP4- and HLA-DR-restricted TH1 cells. Some short peptide-reactive (sp)CD4 T cells showed high functional avidity. Here, we show that a short peptide vaccine is able to activate a specific CD4(+) T-cell repertoire in many patients, facilitating a strong combined CD4(+)/CD8(+) T-cell response.
EVALuna2:19595

Side effect management during immune checkpoint blockade using CTLA-4 and PD-1 antibodies for metastatic melanoma - an update - Kaehler, Katharina C.; Hassel, Jessica C.; Heinzerling, Lucie; Loquai, Carmen; Thoms, Kai-Martin; Ugurel, Selma; Zimmer, Lisa; Gutzmer, Ralf (Journal der Deutschen Dermatologischen Gesellschaft, 2020)
CTLA-4 and PD-1 play a key role in tumor-induced downregulation of lymphocytic immune responses. Immune checkpoint inhibitors have been shown to alter the immune response to various cancer types. Anti-CTLA-4 and anti-PD-1 antibodies affect the interaction between tumor, antigen-presenting cells and T lymphocytes. Clinical studies of the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibodies nivolumab and pembrolizumab have provided evidence of their positive effects on overall survival in melanoma patients. Combined treatment using ipilimumab and nivolumab has been shown to achieve five-year survival rates of 52 %. Such enhancement of the immune response is inevitably associated with adverse events. Knowledge of the spectrum of side effects is essential, both in terms of prevention and management. Adverse events include colitis, dermatitis, hypophysitis, thyroiditis, hepatitis and other, less common autoimmune phenomena. In recent years, considerable progress has been made in the detection and treatment of the aforementioned immune-related adverse events. However, early diagnosis of rare neurological or cardiac side effects, which may be associated with increased mortality, frequently pose a challenge. The present update highlights our current understanding as well as new insights into the spectrum of side effects associated with checkpoint inhibitors and their management.
CRIS-Team WoS Importer:2020-06-16

Siglec-15 on osteoclasts is crucial for bone erosion in serum-Transfer arthritis - Korn, Marina; Schmitt, Heike; Angermüller, Sieglinde; Chambers, David; Seeling, Michaela; Lux, Uwe; Brey, Stefanie; Royzman, Dmytro; Bruckner, Christin; Popp, Vanessa; Percivalle, Elena; Bäuerle, Tobias; et al. (Journal of Immunology, 2020)
Siglec-15 is a conserved sialic acid binding Ig-like lectin, which is expressed on osteoclasts. Deficiency of Siglec-15 leads to an impaired osteoclast development, resulting in a mild osteopetrotic phenotype. The role of Siglec-15 in arthritis is still largely unclear. To address this, we generated Siglec-15 knockout mice and analyzed them in a mouse arthritis model.We could show that Siglec-15 is directly involved in pathologic bone erosion in the K/BxN serum-Transfer arthritis model. Histological analyses of joint destruction provided evidence for a significant reduction in bone erosion area and osteoclast numbers in Siglec-152/2 mice, whereas the inflammation area and cartilage destruction was comparable to wild-Type mice. Thus, Siglec-15 on osteoclasts has a crucial function for bone erosion during arthritis. In addition, we generated a new monoclonal anti Siglec-15 Ab to clarify its expression pattern on immune cells. Whereas this Ab demonstrated an almost exclusive Siglec-15 expression on murine osteoclasts and hardly any other expression on various other immune cell types, human Siglec-15 was more broadly expressed on human myeloid cells, including human osteoclasts. Taken together, our findings show a role of Siglec-15 as a regulator of pathologic bone resorption in arthritis and highlight its potential as a target for future therapies, as Siglec-15 blocking Abs are available.
CRIS-Team Scopus Importer:2020-11-20

Siglec-H-Deficient Mice Show Enhanced Type I IFN Responses, but Do Not Develop Autoimmunity After Influenza or LCMV Infections - Szumilas, Nadine; Corneth, Odilia B.J.; Lehmann, Christian; Schmitt, Heike; Cunz, Svenia; Cullen, Jolie G.; Chu, Talyn; Marosán, Anita; Mócsai, Attila; Benes, Vladimir; Zehn, Dietmar; Dudziak, Diana; et al. (Frontiers in Immunology, 2021)
Siglec-H is a DAP12-associated receptor on plasmacytoid dendritic cells (pDCs) and microglia. Siglec-H inhibits TLR9-induced IFN-α production by pDCs. Previously, it was found that Siglec-H-deficient mice develop a lupus-like severe autoimmune disease after persistent murine cytomegalovirus (mCMV) infection. This was due to enhanced type I interferon responses, including IFN-α. Here we examined, whether other virus infections can also induce autoimmunity in Siglec-H-deficient mice. To this end we infected Siglec-H-deficient mice with influenza virus or with Lymphocytic Choriomeningitis virus (LCMV) clone 13. With both types of viruses we did not observe induction of autoimmune disease in Siglec-H-deficient mice. This can be explained by the fact that both types of viruses are ssRNA viruses that engage TLR7, rather than TLR9. Also, Influenza causes an acute infection that is rapidly cleared and the chronicity of LCMV clone 13 may not be sufficient and may rather suppress pDC functions. Siglec-H inhibited exclusively TLR-9 driven type I interferon responses, but did not affect type II or type III interferon production by pDCs. Siglec-H-deficient pDCs showed impaired Hck expression, which is a Src-family kinase expressed in myeloid cells, and downmodulation of the chemokine receptor CCR9, that has important functions for pDCs. Accordingly, Siglec-H-deficient pDCs showed impaired migration towards the CCR9 ligand CCL25. Furthermore, autoimmune-related genes such as Klk1 and DNase1l3 are downregulated in Siglec-H-deficient pDCs as well. From these findings we conclude that Siglec-H controls TLR-9-dependent, but not TLR-7 dependent inflammatory responses after virus infections and regulates chemokine responsiveness of pDCs.
CRIS-Team Scopus Importer:2021-09-17
Keywords: Interferon-alpha; plasmacytoid dendritic cells; Siglec; SLE; TLR9

Significant differences in patients with a complete insufficiency of the great versus small saphenous vein - Pochec, Katarzyna; Mühlberger, Dominic; Hummel, Thomas; Stücker, Markus; Reich-Schupke, Stefanie (Phlebology, 2019)
Objectives: Most studies on diagnostics and therapy of saphenous veins focus on great saphenous vein or sum up great and small saphenous vein. This study compares patients with an insufficiency of the great saphenous vein versus small saphenous vein. Methods: Prospective study including 50 patients with untreated insufficiency of the great saphenous vein or small saphenous vein, respectively. Patients got a standardised phlebological examination and filled a vein-specific life quality questionnaire (SQOR-V). Results: Great saphenous vein patients were significantly younger (p = 0.001), had more visible varicose veins (p < 0.001), a higher Venous Clinical Severity Score (p = 0.002) and had more symptoms, especially at midday (p = 0.0030) and evening (p = 0.078). They had significantly more concerns about worsening of their varicose veins (p = 0.009) and a vein disease in family members (p = 0.005). Conclusion: Great saphenous vein patients have more and sooner symptoms than small saphenous vein patients. This study discusses if the difference in symptoms is related to the difference in tributaries and a therapy of the tributaries is able to reduce the symptoms.
CRIS-Team Scopus Importer:2019-08-02
Keywords: Chronic venous insufficiency; tributaries; varicose veins; vein therapy; venous symptoms

Silencing β1,2-xylosyltransferase in Transgenic Tomato Fruits Reveals xylose as Constitutive Component of Ige-Binding Epitopes. - Sonnewald, Uwe; Kogel, Karl-Heinz; Pabst, Martin; Paulus, Kathrin; Altmann, Friedrich; Mahler, Vera (Frontiers in Plant Science, 2011)
Complex plant N-glycans containing β1,2-xylose and core α1,3-fucose are regarded as the major class of the so-called "carbohydrate cross-reactive determinants" reactive with IgE antibodies in sera of many allergic patients, but their clinical relevance is still under debate. Plant glycosyltransferases, β1,2-xylosyltransferase (XylT), and core α1,3-fucosyltransferase (FucT) are responsible for the transfer of β1,2-linked xylose and core α1,3-linked fucose residues to N-glycans of glycoproteins, respectively. To test the clinical relevance of β1,2-xylose-containing epitopes, expression of the tomato β1,2-xylosyltransferase was down-regulated by RNA interference (RNAi) in transgenic plants. Fruits harvested from these transgenic plants were analyzed for accumulation of XylT mRNA, abundance of β1,2-xylose epitopes and their allergenic potential. Based on quantitative real-time PCR analysis XylT mRNA levels were reduced up to 10-fold in independent transgenic lines as compared to untransformed control, whereas no xylosylated N-glycans could be revealed by MS analysis. Immunoblotting using anti-xylose-specific IgG antibodies revealed a strong reduction of β1,2-xylose-containing epitopes. Incubating protein extracts from untransformed controls and XylT_RNAi plants with sera from tomato allergic patients showed a patient-specific reduction in IgE-binding, indicating a reduced allergenic potential of XylT_RNAi tomato fruits, in vitro. To elucidate the clinical relevance of β1,2-xylose-containing complex N-glycans skin prick tests were performed demonstrating a reduced responsiveness of tomato allergic patients, in vivo. This study provides strong evidence for the clinical relevance of β1,2-xylose-containing epitopes in vivo.
Keywords: beta 1; 2-xylosyltransferase; RNA interference; tomato allergy; N-glycosylation; CCDs

Similar Impact of Psoriatic Arthritis and Rheumatoid Arthritis on Objective and Subjective Parameters of Hand Function - Liphardt, Anna-Maria; Manger, Eva; Liehr, Sonja; Bieniek, Lisa Maria; Kleyer, Arnd; Simon, David; Tascilar, Koray; Sticherling, Michael; Rech, Jürgen; Schett, Georg; Hueber, Axel (ACR Open Rheumatology, 2020)
ObjectiveThe objective of this study was to compare the impact of psoriatic disease (psoriatic arthritis [PsA] and psoriasis) and rheumatoid arthritis (RA) on objective and subjective parameters of hand function.
CRIS-Team WoS Importer:2021-07-16

Similar Impact of Psoriatic Arthritis and Rheumatoid Arthritis on Objective and Subjective Parameters of Hand Function - Liphardt, Anna-Maria; Manger, Eva; Liehr, Sonja; Bieniek, Lisa; Kleyer, Arnd; Simon, David; Tascilar, Koray; Sticherling, Michael; Rech, Jürgen; Schett, Georg; Hueber, Axel (ARTHRITIS & RHEUMATOLOGY, 2020)
CRIS-Team WoS Importer:2021-01-15

Simultaneous quantification of bone erosions and enthesiophytes in the joints of patients with psoriasis or psoriatic arthritis - effects of age and disease duration - Simon, David; Kleyer, Arnd; Faustini, Francesca; Englbrecht, Matthias; Haschka, Judith; Berlin, Andreas; Kraus, Sebastian; Hueber, Axel; Kocijan, Roland; Sticherling, Michael; Rech, Jürgen; Schett, Georg (Arthritis Research & Therapy, 2018)
BACKGROUND: Comprehensive simultaneous quantification of bone erosion and enthesiophytes in the joints of patients with psoriatic arthritis (PsA) has not been performed. Herein, we aimed to compare the extent of bone erosion and enthesiophytes in patients with PsA, psoriasis (PSO) and healthy controls, assess the influence of age and disease duration on the development of erosions and enthesiophytes and define their impact on physical function. METHODS: Patients with PsA or with PSO and controls were analysed by high-resolution peripheral quantitative computed tomography (HR-pQCT). The extent of bone erosions and enthesiophytes was assessed and plotted according to different categories of age, duration of PSO and duration of PsA, respectively. In addition, demographic and disease-specific data, including physical function (health assessment questionnaire) were collected. RESULTS: A total of 203 patients were analysed; 101 had PsA, 55 had PSO and 47 were healthy individuals. Patients with PsA had significantly more and larger erosions (p = 0.002/p = 0.003) and enthesiophytes (p < 0.001) compared to patients with PSO and healthy controls. Patients with PSO and healthy controls did not differ in erosions, while enthesiophytes were more frequent in patients with PSO than in healthy controls. Bone erosions, but not enthesiophytes, showed strong age-dependency in all three groups. In contrast, enthesiophytes were mostly influenced by the duration of PSO and PsA and, in contrast to bone erosions, were associated with poorer physical function. CONCLUSIONS: Bone erosions are age-dependent, enhanced in PsA and increase with disease duration. Enthesiophytes are less age-dependent, are enhanced in both PSO and PsA and strongly influenced by disease duration. Enthesiophytes impact physical function in PsA suggesting the need for early therapeutic interventions to prevent damage.
EVALuna2:34666

Single-cell Transcriptome Analysis and clonal Kinetics in a Patient after CD19.CAR-T Cell Therapy - Lischer, Christopher; Eisenhauer, Nina; Aigner, Michael; Jacobs, Benedikt; Schletter, M.; Gebhard, C.; Rehli, M.; Bruns, Heiko; Müller, Fabian; Mackensen, Andreas; Vera González, Julio; Völkl, Simon (ONCOLOGY RESEARCH AND TREATMENT, 2022)
CRIS-Team WoS Importer:2022-11-18

Single-Molecule RNA Sequencing Reveals IFN gamma-Induced Differential Expression of Immune Escape Genes in Merkel Cell Polyomavirus-Positive MCC Cell Lines - Sauerer, Tatjana; Lischer, Christopher; Weich, Adrian; Berking, Carola; Vera, Julio; Dörrie, Jan (Frontiers in Microbiology, 2021)
Merkel cell carcinoma (MCC) is a rare and highly aggressive cancer, which is mainly caused by genomic integration of the Merkel cell polyomavirus and subsequent expression of a truncated form of its large T antigen. The resulting primary tumor is known to be immunogenic and under constant pressure to escape immune surveillance. Because interferon gamma (IFN gamma), a key player of immune response, is secreted by many immune effector cells and has been shown to exert both anti-tumoral and pro-tumoral effects, we studied the transcriptomic response of MCC cells to IFN gamma. In particular, immune modulatory effects that may help the tumor evade immune surveillance were of high interest to our investigation. The effect of IFN gamma treatment on the transcriptomic program of three MCC cell lines (WaGa, MKL-1, and MKL-2) was analyzed using single-molecule sequencing via the Oxford Nanopore platform. A significant differential expression of several genes was detected across all three cell lines. Subsequent pathway analysis and manual annotation showed a clear upregulation of genes involved in the immune escape of tumor due to IFN gamma treatment. The analysis of selected genes on protein level underlined our sequencing results. These findings contribute to a better understanding of immune escape of MCC and may help in clinical treatment of MCC patients. Furthermore, we demonstrate that single-molecule sequencing can be used to assess characteristics of large eukaryotic transcriptomes and thus contribute to a broader access to sequencing data in the community due to its low cost of entry.
CRIS-Team WoS Importer:2022-01-28

Sinus Pericranii - Heppt, Franz; Meder, Christine; Wagner, Nicola (Deutsches Ärzteblatt international, 2020)
CRIS-Team WoS Importer:2020-05-05

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells - Düthorn, Alexandra; Turan, Aykut; Drassner, Christina; Muehl-Zurbes, Petra; Heilingloh, Christiane; Steinkasserer, Alexander; Grosche, Linda (Journal of Visualized Experiments, 2019)
Herpes simplex virus type-1 (HSV-1) induces autophagy in both, immature dendritic cells (iDCs) as well as mature dendritic cells (mDCs), whereas autophagic flux is only observed in iDCs. To gain mechanistic insights, we developed efficient strategies to interfere with HSV-1-induced autophagic turnover. An inhibitor-based strategy, to modulate HSV-1-induced autophagy, constitutes the first choice, since it is an easy and fast method. To circumvent potential unspecific off-target effects of such compounds, we developed an alternative siRNA-based strategy, to modulate autophagic turnover in iDCs upon HSV-1 infection. Indeed, electroporation of iDCs with FIP200-specific siRNA prior to HSV-1 infection is a very specific and successful method to ablate FIP200 protein expression and thereby to inhibit autophagic flux. Both presented methods result in the efficient inhibition of HSV-1-induced autophagic turnover in iDCs, whereby the siRNA-based technique is more target specific. An additional siRNA-based approach was developed to selectively silence the protein expression of KIF1 B and KIF2A, facilitating autophagic turnover upon HSV-1 infection in mDCs. In conclusion, the technique of siRNA electroporation represents a promising strategy, to selectively ablate the expression of distinct proteins and to analyze their influence upon an HSV-1 infection.
CRIS-Team WoS Importer:2019-11-15

Sister-Mary-Joseph-Knoten der Brust – Beschreibung einer neuen Entität? - Popp, Judith; Heppt, Markus; Berking, Carola; Heppt, Franz (Journal der Deutschen Dermatologischen Gesellschaft, 2021)
CRIS-Team Scopus Importer:2021-04-23

Six-Color Confocal Immunofluorescence Microscopy with 4-Laser Lines - Heger, Lukas; Lühr, Jennifer J.; Amon, Lukas; Smith, Ana-Suncana; Eissing, Nathalie; Dudziak, Diana (Methods in Molecular Biology, 2021)
Confocal immunofluorescence microscopy is an advanced imaging technique routinely applied in the laboratory and clinics. Histological analyses are performed from tissue material. In general, a single fluorochrome per laser is employed, limiting simultaneous analysis to four antigens in one staining with a conventional 4-laser line microscope. Here, we describe a protocol for combining fluorochromes with the same excitation but different emission properties that allows for the analysis of six different antigens in confocal immunofluorescence microscopy with a conventional 4-laser line microscope. The proposed multiplexed method permits the identification and characterization of complex cell populations in rare tissue material.
CRIS-Team Scopus Importer:2021-10-01
Keywords: DC; Dendritic cells; Fluorochrome; Histology; Multicolor imaging; Tissue

Skin and Soft Tissue Infections Caused by Mycobacterium chelonae: More Common Than Expected? - Uslu, Ugur; Boehm, Olga; Heppt, Franz; Sticherling, Michael (Acta Dermato-Venereologica, 2019)
Mycobacterium chelonae is a rapidly growing non-tuberculous mycobacterium, which causes infections of the human skin and soft tissue. Despite an increasing incidence of such infections, patients are often misdiagnosed. We report here 5 patients with cutaneous and/or soft tissue infection due to M. chelonae who were diagnosed and treated at our centre. Two of the 5 patients were on immunosuppressive treatment. While clinical presentations differed in each patient, all had a long history of skin lesions. In addition to careful history-taking, tissue biopsies were obtained for mycobacterial culture and histopathological examination. Culture-directed antibiotic therapy was initiated, which resulted in a slow, but continuous, healing of the lesions. In summary, M. chelonae infections are still relatively rare, but should be considered in both immunocompromised and immunocompetent patients with prolonged skin lesions resistant to standard antibiotic treatment. For diagnosis, tissue analysis for mycobacterial culture and histopathological examination, and once diagnosed, adequate antibiotic treatment, is needed.
CRIS-Team WoS Importer:2019-09-10

Skin Cancer in Childhood and Adolescents: Treatment and Implications for the Long-Term Follow-Up - Heinzerling, Lucie; Eigentler, Thomas Kurt (Springer International Publishing, 2020)
Skin cancer in childhood and adolescence is rare. Most young patients with cutaneous malignancies have underlying risk factors like a hereditary predisposition or immunosuppression. Rarely, patients present with spontaneous melanoma which can arise from congenital nevi. Treatment for skin cancer is being performed as in adults with the use of the paediatric support structures in addition to dermatooncological care. For medical therapies, e.g. systemic therapy of melanoma, basal or squamous cell carcinoma counselling on fertility has to be implemented as is standard for the younger adults. Since primary skin cancer is often associated with secondary skin cancers, patient education on preventive measures as well as regular clinical controls is crucial to ensure early detection.
CRIS-Team Scopus Importer:2024-12-16
Keywords: Congenital; Excision; Fertility; Melanoma; Non-melanoma skin cancer; Squamous cell carcinoma

Skin lesions may be misleading for final diagnosis – a case of delayed diagnosis and therapy - Meder, Christine; Sticherling, Michael (Journal der Deutschen Dermatologischen Gesellschaft, 2023)
CRIS-Team Scopus Importer:2023-06-09
Keywords: bacterial infections; T cell; virus

Skin symptoms as diagnostic clue for autoinflammatory diseases - Moreira, Alvaro; Torres, Barbara; Peruzzo, Juliano; Mota, Alberto; Eyerich, Kilian; Ring, Johannes (Anais Brasileiros De Dermatologia, 2017)
Autoinflammatory disorders are immune-mediated diseases with increased production of inflammatory cytokines and absence of detectable autoantibodies. They course with recurrent episodes of systemic inflammation and fever is the most common symptom. Cutaneous manifestations are prevalent and important to diagnosis and early treatment of the syndromes. The purpose of this review is to emphasize to dermatologists the skin symptoms present in these syndromes in order to provide their early diagnosis.
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Sklerosierende Hauterkrankungen - Sticherling, Michael (Internist, 2019)
Sclerosing skin manifestations are more a symptom than a diagnosis and must therefore be meticulously clarified. Systemic scleroderma as a multiorgan disease must be distinguished from localized scleroderma or morphea because in addition to a different clinical picture they have a different prognosis and necessitate other therapeutic procedures. Rare sclerosing skin diseases with implications for internal medicine are eosinophilic fasciitis, Buschke’s scleredema adultorum, scleromyxedema and nephrogenic systemic fibrosis.
CRIS-Team Scopus Importer:2019-08-02
Keywords: Mixed connective tissue disease; Morphea; Scleredema adultorum; Scleromyxedema; Systemic scleroderma

Soluble CD83 ameliorates experimental colitis in mice - Eckhardt, Jenny; Kreiser, Simon; Döbbeler, Marina; Nicolette, C.; Debenedette, M. A.; Tcherepanova, I. Y.; Ostalecki, Christian; Pommer, A. J.; Becker, Christoph; Günther, Claudia; Zinser, E.; Mak, T. W.; et al. (Mucosal Immunology, 2014)
The physiological balance between pro- and anti-inflammatory processes is dysregulated in inflammatory bowel diseases (IBD) as in Crohn's disease and ulcerative colitis. Conventional therapy uses anti-inflammatory and immunosuppressive corticosteroids to treat acute-phase symptoms. However, low remission rate and strong side effects of these therapies are not satisfying. Thus, there is a high medical need for new therapeutic strategies. Soluble CD83, the extracellular domain of the transmembrane CD83 molecule, has been reported to have interesting therapeutic and immunosuppressive properties by suppressing dendritic cell (DC)-mediated T-cell activation and inducing tolerogenic DCs. However, the expression and function of CD83 in IBD is still unknown. Here, we show that CD83 expression is upregulated by different leukocyte populations in a chemical-induced murine colitis model. Furthermore, in this study the potential of sCD83 to modulate colitis using an experimental murine colitis model was investigated. Strikingly, sCD83 ameliorated the clinical disease symptoms, drastically reduced mortality, and strongly decreased inflammatory cytokine expression in mesenteric lymph nodes and colon. The infiltration of macrophages and granulocytes into colonic tissues was vigorously inhibited. Mechanistically, we could show that sCD83-induced expression of indolamine 2,3-dioxygenase is essential for its protective effects.
EVALuna2:1840

Soluble CD83 improves and accelerates wound healing by the induction of pro-resolving macrophages - Royzman, Dmytro; Peckert-Maier, Katrin; Stich, Lena; König, Christina; Wild, Andreas; Tauchi, Miyuki; Ostalecki, Christian; Kiesewetter, Franklin; Seyferth, Stefan; Lee, Geoffrey; Eming, Sabine A.; Fuchs, Maximilian; et al. (Frontiers in Immunology, 2022)
To facilitate the recovery process of chronic and hard-to-heal wounds novel pro-resolving treatment options are urgently needed. We investigated the pro-regenerative properties of soluble CD83 (sCD83) on cutaneous wound healing, where sCD83 accelerated wound healing not only after systemic but also after topical application, which is of high therapeutic interest. Cytokine profile analyses revealed an initial upregulation of inflammatory mediators such as TNFα and IL-1β, followed by a switch towards pro-resolving factors, including YM-1 and IL-10, both expressed by tissue repair macrophages. These cells are known to mediate resolution of inflammation and stimulate wound healing processes by secretion of growth factors such as epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF), which promote vascularization as well as fibroblast and keratinocyte differentiation. In conclusion, we have found strong wound healing capacities of sCD83 beyond the previously described role in transplantation and autoimmunity. This makes sCD83 a promising candidate for the treatment of chronic- and hard-to-heal wounds.
CRIS-Team Scopus Importer:2022-10-28
Keywords: CD83; macrophages; stem cells; therapy; tissue regeneration; wound healing

Soluble CD83 inhibits skin inflammation to chemical sensitizers - Mihatsch, P.; Boyd, P.; Krzyzak, Lena; Lechmann, Matthias; Nicolas, J.; Mahler, Vera; Steinkasserer, Alexander; Vocanson, Marc (2016)
EVALuna2:26037

Soluble CD83 Inhibits T Cell Activation by Binding to the TLR4/MD-2 Complex on CD14(+) Monocytes - Horvatinovich, Joe M.; Grogan, Elizabeth W.; Norris, Marcus; Steinkasserer, Alexander; Lemos, Henrique; Mellor, Andrew L.; Tcherepanova, Irina Y.; Nicolette, Charles A.; Debenedette, Mark A. (Journal of Immunology, 2017)
The transmembrane protein CD83, expressed on APCs, B cells, and T cells, can be expressed as a soluble form generated by alternative splice variants and/or by shedding. Soluble CD83 (sCD83) was shown to be involved in negatively regulating the immune response. sCD83 inhibits T cell proliferation in vitro, supports allograft survival in vivo, prevents corneal transplant rejection, and attenuates the progression and severity of autoimmune diseases and experimental colitis. Although sCD83 binds to human PBMCs, the specific molecules that bind sCD83 have not been identified. In this article, we identify myeloid differentiation factor-2 (MD-2), the coreceptor within the TLR4/MD-2 receptor complex, as the high-affinity sCD83 binding partner. TLR4/MD-2 mediates proinflammatory signal delivery following recognition of bacterial LPSs. However, altering TLR4 signaling can attenuate the proinflammatory cascade, leading to LPS tolerance. Our data show that binding of sCD83 to MD-2 alters this signaling cascade by rapidly degrading IL-1R-associated kinase-1, leading to induction of the anti-inflammatory mediators IDO, IL-10, and PGE2 in a COX-2-dependent manner. sCD83 inhibited T cell proliferation, blocked IL-2 secretion, and rendered T cells unresponsive to further downstream differentiation signals mediated by IL-2. Therefore, we propose the tolerogenic mechanism of action of sCD83 to be dependent on initial interaction with APCs, altering early cytokine signal pathways and leading to T cell unresponsiveness.
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Soluble CD83 modulates human-monocyte-derived macrophages toward alternative phenotype, function, and metabolism. - Peckert-Maier, Katrin; Wild, Andreas; Sprißler, Laura; Fuchs, Maximilian; Beck, Philipp; Auger, Jean-Philippe; Sinner, Pia; Strack, Astrid; Mühl-Zürbes, Petra; Ramadan, Ntilek; Kunz, Meik; Krönke, Gerhard; et al. (Frontiers in Immunology, 2023)
Alterations in macrophage (Mφ) polarization, function, and metabolic signature can foster development of chronic diseases, such as autoimmunity or fibrotic tissue remodeling. Thus, identification of novel therapeutic agents that modulate human Mφ biology is crucial for treatment of such conditions. Herein, we demonstrate that the soluble CD83 (sCD83) protein induces pro-resolving features in human monocyte-derived Mφ biology. We show that sCD83 strikingly increases the expression of inhibitory molecules including ILT-2 (immunoglobulin-like transcript 2), ILT-4, ILT-5, and CD163, whereas activation markers, such as MHC-II and MSR-1, were significantly downregulated. This goes along with a decreased capacity to stimulate alloreactive T cells in mixed lymphocyte reaction (MLR) assays. Bulk RNA sequencing and pathway analyses revealed that sCD83 downregulates pathways associated with pro-inflammatory, classically activated Mφ (CAM) differentiation including HIF-1A, IL-6, and cytokine storm, whereas pathways related to alternative Mφ activation and liver X receptor were significantly induced. By using the LXR pathway antagonist GSK2033, we show that transcription of specific genes (e.g., PPARG, ABCA1, ABCG1, CD36) induced by sCD83 is dependent on LXR activation. In summary, we herein reveal for the first time mechanistic insights into the modulation of human Mφ biology by sCD83, which is a further crucial preclinical study for the establishment of sCD83 as a new therapeutical agent to treat inflammatory conditions.
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Soluble CD83 promotes cutaneous wound healing in an IDO-and beta-catenindependent manner - Royzman, Dmytro; Peckert-Maier, K.; Stich, L.; Wild, Andreas; Ostalecki, C.; Kiesewetter, Franklin; Seyferth, Stefan; Lee, Geoffrey; Eming, S. A.; Berking, Carola; Zinser, Elisabeth; Steinkasserer, Alexander (EXPERIMENTAL DERMATOLOGY, 2022)
CRIS-Team WoS Importer:2022-03-04

Soluble CD83 Triggers Resolution of Arthritis and Sustained Inflammation Control in IDO Dependent Manner - Royzman, Dmytro; Andrev, Darja; Stich, Lena; Rauh, Manfred; Bäuerle, Tobias; Ellmann, Stephan; Boon, Louis; Kindermann, Markus; Peckert, Katrin; Bozec, Aline; Schett, Georg; Steinkasserer, Alexander; et al. (Frontiers in Immunology, 2019)
Interference with autoimmune-mediated cytokine production is a key yet poorly developed approach to treat autoimmune and inflammatory diseases such as rheumatoid arthritis. Herein, we show that soluble CD83 (sCD83) enhances the resolution of autoimmune antigen-induced arthritis (AIA) by strongly reducing the expression levels of cytokines such as IL-17A, IFN gamma, IL-6, and TNF alpha within the joints. Noteworthy, also the expression of RANKL, osteoclast differentiation, and joint destruction was significantly inhibited by sCD83. In addition, osteoclasts which were cultured in the presence of synovial T cells, derived from sCD83 treated AIA mice, showed a strongly reduced number of multinuclear large osteoclasts compared to mock controls. Enhanced resolution of arthritis by sCD83 was mechanistically based on IDO, since inhibition of IDO by 1-methyltryptophan completely abrogated sCD83 effects on AIA. Blocking experiments, using anti-TGF-beta antibodies further revealed that also TGF-beta is mechanistically involved in the sCD83 induced reduction of bone destruction and cartilage damage as well as enhanced resolution of inflammation. Resolution of arthritis was associated with increased numbers of regulatory T cells, which are induced in a sCD83-IDO-TGF-beta dependent manner. Taken together, sCD83 represents an interesting approach for downregulating cytokine production, inducing regulatory T cells and inducing resolution of autoimmune arthritis.
CRIS-Team WoS Importer:2019-04-12

Sonnenschutz, Stahl, Strahl, Salbe und Systemtherapie - Berking, Carola; Szeimies, R. M. (Hautarzt, 2020)
CRIS-Team Scopus Importer:2020-08-07

SOX10-based drug repurposing identifies novel therapeutic targets in uveal melanoma - Wessely, A.; Kammerbauer, C.; Lischer, Christopher; Weich, A.; Vera, Julio; Berking, Carola; Heppt, Markus (JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, 2022)
CRIS-Team WoS Importer:2022-09-23

Späte Diagnose einer subkutanen Dirofilariose nach einem Mückenstich in Deutschland - Uslu, Ugur; Jahn, Julia; Erdmann, Michael (Journal der Deutschen Dermatologischen Gesellschaft, 2017)
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Spätfolgen nach Immuntherapie: Immunvermittelte Nebenwirkungen von Checkpointinhibitoren - Duong, Sophie L.; Zierold, Sarah; Kramer, Rafaela; Reincke, Martin; Kerl-French, Katrin; Boehmerle, Wolfgang; Pavel, Marianne Ellen; Weckbach, Ludwig; French, Lars E.; Knauss, Samuel; Heinzerling, Lucie (Onkologe, 2021)
Background: Immune checkpoint inhibitors (ICIs) are potent immunotherapeutic agents for many tumor entities. However, ICIs can induce immune-related adverse events (irAE) that can potentially affect any organ system, causing life-changing sequelae or even death. These irAEs can occur months after termination of immunotherapy and long-term effects may persist for years after finishing therapy. Due to expanding clinical indications for ICIs including therapy in earlier tumor stages, the risk–benefit analysis needs to take into account these long-term side effects. Objectives: The sequelae of ICI therapy are reviewed and the international online registry Side Effect Registry Immuno-Oncology (SERIO) for the unified collection and characterization of irAEs is introduced. Materials and methods: We analyzed data from SERIO and performed a selective literature search in the databases PubMed, Cochrane Central Register of Controlled Trials and Google Scholar to characterize, analyze and summarize long-term sequelae of irAE induced by ICI therapy. Results: The most commonly observed irAEs with long-term sequelae involve the skin (leucotrichia, melanoma-associated hypopigmentation) and endocrine irAEs (thyroiditis, hypophysitis, adrenalitis and diabetes). While the former is especially stigmatizing, endocrine irAEs usually require long-term hormone substitution. Neurologic and cardiologic irAEs are relatively rare, but they are associated with severe complications leading to increased morbidity and mortality. Conclusions: Until now, prospective data about long-term consequences of irAEs are lacking. The SERIO registry addresses this need as irAEs are collected to enable long-term follow-up and optimized management.
CRIS-Team Scopus Importer:2021-05-21
Keywords: Benefit-risk assessment; Data collection; Hypopigmentation; Neoplasms; Registries

Spatial cell graph analysis reveals skin tissue organization characteristic for cutaneous T cell lymphoma - Sarkar, Suryadipto; Möller, Anna; Hartebrodt, Anne; Erdmann, Michael; Ostalecki, Christian; Baur, Andreas; Blumenthal, David B. (npj Systems Biology and Applications, 2024)

Spatial Single Cell Profiling Using Imaging Mass Cytometry: Inflammatory Versus Penetrating Crohn's Disease - Lehmann, Malte; Weixler, Benjamin; Elezkurtaj, Sefer; Loddenkemper, Christopher; Atreya, Imke; Atreya, Raja; Bacher, Petra; Becker, Christoph; Bojarski, Christian; Britzen-Laurent, Nathalie; Bosch-Voskens, Caroline; Chang, Hyun Dong; et al. (Journal of Crohns & Colitis, 2024)
Background and Aims: Fistula formation is a major complication in Crohn's disease [CD] and the role of the immune cell compartment remains to be elucidated. Thus, we compared the immune cell compartment of CD fistula to inflammatory CD colitis using imaging mass cytometry [IMC] and immunofluorescence. Methods: A 36-marker panel including structural, functional, and lineage markers for use in IMC was established. This panel was applied to analyse paraffin-embedded CD fistula tract [n = 11], CD colitis [n = 10], and colon samples from non-inflamed controls [n = 12]. Computational methods for cell segmentation, dimensionality reduction, and cell type clustering were used to define cell populations for cell frequency, marker distribution, and spatial neighbourhood analysis. Multiplex immunofluorescence was used for higher resolution spatial analysis. Results: Analysis of cell frequencies in CD fistulas compared to CD colitis and control colonic samples revealed a significant increase in neutrophils, effector cytotoxic T cells, and inflammatory macrophages in CD fistula samples, whereas regulatory T cells were decreased. Neutrophils in CD fistula expressed significantly more matrix metalloproteinase 9 [MMP9], correlating with extracellular matrix remodelling. Neighbourhood analysis revealed a strong association between MMP9+ neutrophils and effector cytotoxic T cells in both CD fistulas and colitis. Conclusions: This study presents the first highly multiplexed single cell analysis of the immune cell compartment of CD fistulas and their spatial context. It links immune cell dynamics, particularly MMP9+ neutrophils, to extracellular matrix remodelling in CD fistulas, offering insights into the complex network of cellular interactions and potential therapeutic targets for CD complications.
CRIS-Team Scopus Importer:2024-09-13
Keywords: fistula; imaging mass cytometry; Penetrating Crohn's disease

Spatial, structural and density determinants of DC:T cell interaction under immunostimulatory conditions - Vurnek, D.; Amon, Lukas; Buttazzo, L.; Lehmann, C.; Zaburdaev, Vasily; Dudziak, Diana (EUROPEAN JOURNAL OF IMMUNOLOGY, 2022)
CRIS-Team WoS Importer:2023-01-27

Specific dermatoses of pregnancy - Ambros-Rudolph, C. M.; Sticherling, Michael (Hautarzt, 2017)
The specific dermatoses of pregnancy represent a heterogeneous group of inflammatory skin diseases related to pregnancy and/or the postpartum period. A clinically relevant classification has been well established over the past 10 years and includes pemphigoid gestationis, polymorphic eruption of pregnancy, intrahepatic cholestasis of pregnancy, and atopic eruption of pregnancy. The hallmark of all four entities is severe pruritus that is accompanied by characteristic skin changes. While some of these dermatoses are distressing only to the mother because of pruritus, others may be associated with significant fetal risks. Early diagnosis and prompt treatment are therefore essential. In this review, we discuss in detail pemphigoid gestationis, polymorphic and atopic eruptions of pregnancy whereas intrahepatic cholestasis of pregnancy is discussed in a separate article (Kremer A, Ständer S, DOI 10.1007/s00105-016-3923-y ). Furthermore, we present a helpful algorithm for diagnosis and management of pruritus in pregnancy.
EVALuna2:34362

Specific phenotype and function of CD56-expressing innate immune cell subsets in human thymus - Gerstner, Stephanie; Köhler, Wolfgang; Heidkamp, Gordon Frederik; Purbojo, Ariawan; Uchida, Shizuka; Ekici, Arif Bülent; Heger, Lukas; Luetke-Eversloh, Merlin; Schubert, Ralf; Bader, Peter; Klingebiel, Thomas; Koehl, Ulrike; et al. (Journal of Leukocyte Biology, 2016)
Whereas innate immune cells, such as NK and innate lymphoid cells (ILCs), have been characterized in different human tissues, knowledge on the thymic CD56-expressing cell subsets is limited. In this study, the rare subpopulations of thymic CD56(+)CD3(-) cells from samples of >100 patients have been successfully analyzed. The results revealed fundamental differences between thymic and peripheral blood (PB) CD56(+)CD3(-) cells. Thymic tissues lacked immunoregulatory CD56(high)CD16(dim) NK cells but showed two Eomes(+)CD56(dim) subsets on which common NK cell markers were significantly altered. CD56(dim)CD16(high) cells expressed high amounts of NKG2A, NKG2D, and CD27 with low CD57. Conversely, CD56(dim)CD16(dim) cells displayed high CD127 but low expression of KIR, NKG2D, and natural cytotoxicity receptors (NCRs). Thymic CD56(+)CD3(-) cells were able to gain cytotoxicity but were especially immunoregulatory cells, producing a broad range of cytokines. Finally, one population of thymic CD56(+) cells resembled conventional NK cells, whereas the other represented a novel, noncanonical NK subset.
EVALuna2:9311

Spectrum of peristomal Dermatoses - Dietmaier, Louisa; Summa, S.; Erfurt-Berge, Cornelia (JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, 2021)
CRIS-Team WoS Importer:2021-04-16

Spontaneous regression rates of actinic keratosis: a systematic review and pooled analysis of randomized controlled trials. - Steeb, Theresa; Petzold, Anne; Hornung, Annkathrin; Wessely, Anja; Berking, Carola; Heppt, Markus (Scientific Reports, 2022)
Actinic keratosis (AK) are precancerous lesions of the skin which may progress to invasive squamous cell carcinoma. However, single lesions may also persist or even regress and heal spontaneously. Until now, evidence on the natural course of AK including spontaneous regression is limited. We aimed to synthesize regression rates of AK. We performed a systematic literature research in Medline, Embase, and CENTRAL for eligible trials until 3rd March 2020. Spontaneous regression rates were pooled using a random-effects model to calculate pooled proportions of participant-specific and lesion-specific complete clearance rates reported for the placebo arms of randomized controlled trials. Subgroup analyses were performed to dissect differences according to the type of placebo, immunocompetence of the participants, and localization of the lesions. Data from 38 records was included. The pooled participant-specific clearance rate was 8% (95% CI 6-10%, I2 = 71%) while the lesion-specific clearance rate was 23% (95% CI 16-31%, I2 = 97%). The highest participant- and lesion-specific clearance rates were achieved 12 weeks after the end of treatment (12% and 33%, respectively). Subgroup analysis revealed participant- as well as lesion-specific clearance rates of 0% for organ transplant recipients (OTR). We conclude that only a few participants achieve complete regression of their AK without any active treatment. Besides, the results underline that lesion clearance without active treatment is unlikely in OTR. Thus, early and consequent treatment of AK is recommended. Special attention should be paid when treating AK of OTR.
EVALuna2:502113

Squamous cell carcinomas in chronic venous leg ulcers. Data of the German Marjolin Registry and review - Reich-Schupke, Stefanie; Doerler, Martin; Wollina, Uwe; Dissemond, Joachim; Horn, Thomas; Stroelin, Anke; Stuecker, Markus; Erfurt-Berge, Cornelia (Journal der Deutschen Dermatologischen Gesellschaft, 2015)
Background: Secondary squamous cell carcinoma (SCC) is a rare complication of chronic venous leg ulcers. So far, little is known about its pathophysiology and clinical behavior. Initiated by the working group "Wound Healing" (AGW) of the German Society of Dermatology (DDG), it is the objective of the current Marjolin registry to collect cases of SCC arising in venous ulcers, in order to evaluate diagnostic characteristics. Patients and Methods: All members of the AGW received questionnaires inquiring about basic patient data, ulcer characteristics, and therapy conducted. Results: From 2010 to 2013, 30 patients (20 women, 10 men) from six tertiary wound care centers were registered. Mean age was 76.17 years. The average duration of venous leg ulcers prior to SCC diagnosis was 15.93 years. Suspicious wound characteristics primarily included: pain (n = 3), therapy resistance (n = 27), and fetor (n = 12) as well as clinical appearance (n = 10) with atypical morphology, nodular wound bed, and hypergranulation. Conclusions: Atypical morphology or changes in appearance as well as therapy resistance despite optimal care (6-12 weeks) should prompt physicians to take spindle-shaped, if necessary multiple and serial, biopsies. Primary risk factors for malignant transformation include patient age and ulcer duration.
EVALuna2:19577

Stability and activity of MCSP-specific chimeric antigen receptors (CARs) depend on the scFv antigen-binding domain and the protein backbone - Krug, Christian; Birkholz, Katrin; Paulus, Alexander; Schwenkert, Michael; Schmidt, Patrick; Hoffmann, Nicole; Hombach, Andreas; Fey, Georg; Abken, Hinrich; Schuler, Gerold; Schuler-Thurner, Beatrice; Dörrie, Jan; et al. (Cancer Immunology Immunotherapy, 2015)
Chimeric antigen receptor (CAR)-modified T cells emerged as effective tools in the immunotherapy of cancer but can produce severe on-target off-tissue toxicities. This risk can conceivably be overcome, at least partially, by transient transfection. The design of CARs, however, has so far not been optimized for use in non-permanent T cell modification. Here we compared the performance of T cells modified with three different first- and second-generation CARs, each specific for MCSP (HMW-MAA) which is commonly expressed by melanoma cells. Upon RNA transfer, the expression of all receptors was limited in time. The second-generation CARs, which combined CD28-CD3ζ signaling, were expressed at higher levels and more prolonged than first-generation CARs with CD3ζ only. The CD28 domain increased the cytokine production, but had only an indirect effect on the lytic capacity, by prolonging the CAR expression. Especially for the second-generation CARs, the scFv clearly impacted the level and duration of CAR expression and the T cell performance. Thus, we identified a CAR high in both expression and anti-tumor cell reactivity. T cells transfected with this CAR increased the mean survival time of mice after challenge with melanoma cells. To facilitate clinical application, this CAR was used to redirect T cells from late-stage melanoma patients by RNA transfection. These T cells mediated effective antigen-specific tumor cell lysis and release of pro-inflammatory cytokines, even after cryoconservation of the transfected T cells. Taken together, the analysis identified a CAR with superior anti-melanoma performance after RNA transfer which is a promising candidate for clinical exploration.
EVALuna2:19545

Standardized Computer-Assisted Analysis of PRAME Immunoreactivity in Dysplastic Nevi and Superficial Spreading Melanomas - Koch, Elias; Erdmann, Michael; Berking, Carola; Kiesewetter, Franklin; Kramer, Rafaela; Schliep, Stefan; Heppt, Markus (International Journal of Molecular Sciences, 2023)
PRAME (PReferentially expressed Antigen in MElanoma) is a cancer testis antigen that is frequently expressed in melanoma compared to benign melanocytic proliferations and nevi. However, the interpretation of the intensity and distribution of PRAME immunostaining is not standardized a lot, which makes interpretation difficult. PRAME-stained histological slides of superficial spreading melanomas (SSM) and dysplastic nevi (DN) were digitized and analyzed using the digital pathology and image platform QuPath. t-tests and ROC AUCs were performed with SPSS. A p-value of <0.05 was used for statistical significance, and a ROC AUC score of >0.8 was considered a good result. A cut-off score was defined in an evaluation cohort and subsequently analyzed in an independent validation cohort. In total, 81 PRAME-stained specimens were included. The evaluation cohort included 32 (50%) SSM and 32 (50%) DN, and the mean of PRAME-positive cells/mm2 for the entire lesion was 455.3 (SD 428.2) in SSM and 60.5 (SD 130.1; p < 0.001) in DN. The ROC AUC of PRAME-positive cells of the entire lesion was 0.866, and in the epidermis it was 0.901. The defined cut-off score to distinguish between DN and SSM was 97.67 cells/mm2. In the validation cohort, 16 out of 17 cases (94.1%) were correctly classified by the cut-off score. The computer-aided assessment of PRAME immunostaining is a useful tool in dermatopathology to distinguish between DN and SSM. Lesions with a moderate expression and indifferent morphologic features will remain a challenge for dermatopathologists.
CRIS-Team Scopus Importer:2023-04-21
Keywords: computer-assisted analysis; dysplastic nevus; immunohistochemistry; melanoma; PRAME

Status report on the atopic dermatitis registry TREATgermany Statusbericht zum Neurodermitisregister TREATgermany - Siegels, D.; Haufe, E.; Heinrich, L.; Werfel, T.; Weidinger, S.; Schmitt, Jochen; Abraham, S.; Asefi, M.; Asmussen, Andrea; Augustin, M.; Bell, Magnus; Bieber, T.; et al. (Allergologie, 2021)
CRIS-Team Scopus Importer:2021-10-22
Keywords: Atopic dermatitis; Atopic eczema; Clinical registry; Clinical symptom severity; Systemic treatment

Stellenwert der Biopsie in der Diagnostik chronischer Wunden – ein Positionspapier der Initiative Chronische Wunden (ICW) e. V. - Erfurt-Berge, Cornelia; Bültemann, A.; Gerber, V.; Motzkus, M.; Rembe, J. D.; Dissemond, J. (Die Dermatologie, 2023)
Diagnostic assessment of chronic wounds is essential for the initiation of causal therapeutic treatment. For diagnostic classification of the wound genesis, it may be necessary to take a tissue sample for histological and/or microbiological processing. If there is clinical suspicion of a specific cause of the wound such as a neoplasm, an inflammatory dermatosis or a pathogen-induced wound, a tissue sample for further diagnosis is required immediately. If the ulceration does not respond sufficiently to adequate causal therapy, a tissue sample for further evaluation is recommended after 12 weeks. The choice of the correct sampling technique, further storage, transport and processing are just as decisive for a reliable result as the specific question for the diagnostic laboratory.
CRIS-Team Scopus Importer:2023-12-15
Keywords: Differential diagnosis; Histology; Leg ulcer; Microbiology; Tissue sample

Step-by-step Improvement of mRNA-electroporated dendritic Cells in a Phase I / II Clinical Study in cutaneous Melanoma Patients: better Survival correlates with a higher Immunoscore and increased Expression of PEBP1 in the Blood - Dörrie, Jan; Schaft, Niels; Gross, S.; Ostalecki, Christian; Eberhardt, Martin; Vera-Gonzales, J.; Uslu, Ugur; Moreira, Alvaro; Koch, Elias; Kummer, Mirko; Erdmann, M.; Schliep, S.; et al. (JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, 2020)
CRIS-Team WoS Importer:2020-09-11

Stereotactic radiation therapy for liver metastases: factors affecting local control and survival. - Andratschke, Nicolaus H. J.; Nieder, Carsten; Heppt, Franz; Molls, Michael; Zimmermann, Frank (Radiation Oncology, 2015)
To report on outcome and toxicity of stereotactic body radiotherapy (SBRT) for liver metastases in patients not eligible for surgery.From 2000 to 2009, 74 patients with 91 liver metastases from different primaries have been treated with SBRT at our institution. Median planning target volume was 123 ccm (range: 10.6-1074 ccm). Treatment consisted of 3-5 fractions with 5-12.5 Gy/ fraction prescribed to the surrounding 60-95% isodose with daily image guidance. Regular follow-up included CT or MRI imaging until tumor progression.Median local recurrence-free interval was 23 months with a local control rate of 74.7%, 48.3% and 48.3% after 1, 2 and 3 years. Only minimum biologically effective dose (BED) to gross tumor volume (GTV) remained as independent significant factor for local control in multivariate analysis. No local recurrences were observed in lesions (n = 12) which received a minimal BED to the GTV of 120 Gy. Including 26 local recurrences, 67 patients (91%) showed disease progression after SBRT with a median time of 5 months. Median overall survival was 27 months with survival rates of 77%, 30% and 27% at 1, 3 and 5 years. On multivariate analysis only GTV volume remained as independent significant prognostic factor for overall survival (p = 0.002). No grade 3 to 5 acute toxicity and no grade 4 or 5 late toxicity occurred.SBRT for liver metastases was well tolerated in this non-selected patient cohort and yielded good local control despite the considerable size of most lesions treated. Long-term survival is possible after SBRT.
EVALuna2:86702

Stereotactic radiosurgery and combined immune checkpoint therapy with ipilimumab and nivolumab in patients with melanoma brain metastases: A retrospective monocentric toxicity analysis - Bodensohn, Raphael; Werner, Simone; Reis, Jonas; Pazos Escudero, Montserrat; Kaempfel, Anna Lena; Hadi, Indrawati; Forbrig, Robert; Manapov, Farkhad; Corradini, Stefanie; Belka, Claus; Theurich, Sebastian; Heinzerling, Lucie; et al. (Clinical and Translational Radiation Oncology, 2023)
Purpose and objective: Adding stereotactic radiosurgery (SRS) to combined immune checkpoint therapy with ipilimumab and nivolumab (IPI + NIVO) has led to promising results for patients with melanoma brain metastases (MBM). This study retrospectively analyzes the toxicity profile depending on the timing of SRS with regard to IPI + NIVO. Materials and methods: For this study, the clinical database was searched for all patients with MBM who were treated with SRS and IPI + NIVO. The patients were separated into three groups: group A completed IPI + NIVO (usually up to four cycles) >14 days before SRS, in group B IPI + NIVO was initiated>14 days after SRS, and group C received SRS concurrently to IPI + NIVO. Treatment related toxicity was obtained from clinical and neuroradiological records. Analyses were performed using the Fisher-Yates-test. Results: 31 patients were assessed including six (19.4 %), seven (22.6 %) and 18 (58.1 %) patients, in groups A, B and C, respectively. Baseline prognostic markers between groups were balanced. In total, five (16.1 %) patients experienced neurological grade 3 toxicities related to SRS. All of these five patients were in group C, which was near-significantly correlated with a risk for grade 3 toxicities (p = 0.058). Post-hoc analyses showed that a maximum time period of seven days between SRS and IPI + NIVO was significantly correlated with grade 3 toxicity (p = 0.048). Conclusion: Application of SRS to IPI + NIVO within a seven-day span was related to higher toxicity rates in this retrospective analysis. After previous studies focused on immune checkpoint monotherapies with SRS and declared it as safe, this study indicates that concomitant application of IPI + NIVO and SRS might increase side effects. Prospective validation is warranted to corroborate these findings.
CRIS-Team Scopus Importer:2023-01-27
Keywords: Checkpoint inhibition; Intracranial hemorrhage; Ipilimumab; Nivolumab; Radiation necrosis; Side effects; Stereotactic radiosurgery

Still Alive and Kicking: In-Vitro-Generated GM-CSF Dendritic Cells! - Lutz, Manfred B.; Inaba, Kayo; Schuler, Gerold; Romani, Nikolaus (Immunity, 2016)
EVALuna2:19572

Stoma care in pyoderma gangrenosum - Summa, Scarlett; Hofmann, Gabriele; Erfurt-Berge, Cornelia (Coloproctology, 2021)
Pyoderma gangrenosum is a rare inflammatory skin disorder presenting with ulcerations. Peristomal pyoderma gangrenosum confronts the treating physician with diagnostic and therapeutic challenges. Pyoderma gangrenosum is often not recognized early enough but an interdisciplinary treatment approach should be initiated as soon as possible as wound care alone will not lead to healing of these skin alterations. Wound care in combination with stoma care is often difficult in these cases and with unreliable obturation of stoma and infiltration of the skin protection materials it is associated with impairments in the quality of life of the person affected. The aim of wound care is to protect the wound from stoma leakage and to ensure sufficient stoma care by changing the materials for stoma care at regular intervals.
CRIS-Team WoS Importer:2021-12-31

Stringent monitoring can decrease mortality of immune checkpoint inhibitor induced cardiotoxicity - Wang, Ying; Ertl, Carolin; Schmitt, Christina; Hammann, Linda; Kramer, Rafaela; Grabmaier, Ulrich; Schöberl, Florian; Anz, David; Piseddu, Ignazio; Pesch, Giulia; Vera, Julio; Froehlich, Waltraud; et al. (Frontiers in Cardiovascular Medicine, 2024)
Background: Immune checkpoint inhibitor (ICI)-induced myocarditis is a rare immune-related adverse event (irAE) with a fatality rate of 40%–46%. However, irMyocarditis can be asymptomatic. Thus, improved monitoring, detection and therapy are needed. This study aims to generate knowledge on pathogenesis and assess outcomes in cancer centers with intensified patient management. Methods: Patients with cardiac irAEs from the SERIO registry (www.serio-registry.org) were analyzed for demographics, ICI-related information (type of ICI, therapy line, combination with other drugs, onset of irAE, and tumor response), examination results, irAE treatment and outcome, as well as oncological endpoints. Cardiac biopsies of irMyocarditis cases (n = 12) were analyzed by Nanostring and compared to healthy heart muscle (n = 5) and longitudinal blood sampling was performed for immunophenotyping of irMyocarditis-patients (n = 4 baseline and n = 8 during irAE) in comparison to patients without toxicity under ICI-therapy (n = 4 baseline and n = 7 during ICI-therapy) using flow cytometry. Results: A total of 51 patients with 53 cardiac irAEs induced by 4 different ICIs (anti-PD1, anti-PD-L1, anti-CTLA4) were included from 12 centers in 3 countries. Altogether, 83.0% of cardiac irAEs were graded as severe or life-threatening, and 11.3% were fatal (6/53). Thus, in centers with established consequent troponin monitoring, work-up upon the rise in troponin and consequent treatment of irMyocarditis with corticosteroids and –if required–second-line therapy mortality rate is much lower than previously reported. The median time to irMyocarditis was 36 days (range 4–1,074 days) after ICI initiation, whereas other cardiotoxicities, e.g. asystolia or myocardiopathy, occurred much later. The cytokine-mediated signaling pathway was differentially regulated in myocardial biopsies as compared to healthy heart based on enrichment Gene Ontology analysis. Additionally, longitudinal peripheral blood mononuclear cell (PBMC) samples from irMyocarditis-patients indicated ICI-driven enhanced CD4+ Treg cells and reduced CD4+ T cells. Immunophenotypes, particularly effector memory T cells of irMyocarditis-patients differed from those of ICI-treated patients without side effects. LAG3 expression on T cells and PD-L1 expression on dendritic cells could serve as predictive indicators for the development of irMyocarditis. Conclusion: Interestingly, our cohort shows a very low mortality rate of irMyocarditis-patients. Our data indicate so far unknown local and systemic immunological patterns in cardiotoxicity.
CRIS-Team Scopus Importer:2024-06-28
Keywords: cardiovascular toxicity; checkpoint inhibitor; immunotherapy; melanoma; myocarditis

Strong and sustained effector function of memory- versus naïve-derived T cells upon T-cell receptor RNA transfer: Implications for cellular therapy - Thomas, Simone; Klobuch, Sebastian; Besold, Katrin; Plachter, Bodo; Dörrie, Jan; Schaft, Niels; Theobald, Matthias; Herr, Wolfgang (European Journal of Immunology, 2012)
Current protocols used to select CMV-specific T cells for adoptive immunotherapy focus on virus-specific memory T cells from seropositive donors. However, this strategy is not feasible in patients undergoing allogeneic haematopoietic stem-cell transplantation (HSCT) from CMV-seronegative donors. Here, we redirected T cells of CMV-seronegative donors with a human genetically engineered TCR recognizing an HLA-A*0201-binding peptide epitope of CMVpp65. To facilitate clinical translation of this approach, we used a non-viral expression system based on in vitro transcribed RNA and electroporation. Although memory and naïve-derived T-cell subsets were both efficiently transfected by TCR-RNA, memory-derived T cells showed much stronger levels of HLA-A*0201-restricted cytolytic activity to CMV-infected fibroblasts and maintained acquired function for 5-10 days. In addition to redirection of CD8+ cytotoxic T cells, TCR-RNA transfection was capable of redirecting CD4+ T cells into potent Ag-specific Th cells that efficiently triggered maturation of DCs. Our data suggest that memory rather than naïve-derived T cells are the preferred subset for transient TCR expression by RNA electroporation, providing more efficient and sustained virus-specific CD4+ and CD8+ T-cell function. CMV TCR-RNA may represent a suitable therapeutic 'off-the-shelf' reagent to be used in severe CMV infections of HSCT patients when endogenous CMV-specific T-cell immunity is insufficient. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
CRIS-Team Scopus Importer:2021-10-01
Keywords: Cytomegalovirus; Memory T cells; Naive T cells; RNA; T-cell receptor

STRUCTURAL ENTHESEAL LESIONS IN PSORIASIS PATIENTS ARE ASSOCIATED WITH AN INCREASED RISK OF PROGRESSION TO PSORIATIC ARTHRITIS - A PROSPECTIVE COHORT STUDY - Simon, David; Tascilar, K.; Kleyer, Arnd; Bayat, Sara; Kampylafka, E.; Hueber, Axel; Rech, Jürgen; Schuster, Louis; Engel, K.; Sticherling, Michael; Schett, Georg (ANNALS OF THE RHEUMATIC DISEASES, 2020)
CRIS-Team WoS Importer:2020-08-21

Subclinical joint inflammation in patients with psoriasis without concomitant psoriatic arthritis: a cross-sectional and longitudinal analysis - Faustini, Francesca; Simon, Dominic; Oliveira, Isabelle; Kleyer, Arnd; Haschka, Judith; Englbrecht, Matthias; Cavalcante, Alan Rodrigues; Kraus, Sebastian; Tabosa, Taiane Ponte; Figueiredo, Camille; Hueber, Axel; Kocijan, Roland; et al. (Annals of the Rheumatic Diseases, 2016)
To search for subclinical inflammatory joint disease in patients with psoriasis without psoriatic arthritis (PsA), and to determine whether such changes are associated with the later development of PsA.Eighty-five subjects without arthritis (55 with psoriasis and 30 healthy controls) received high field MRI of the hand. MRI scans were scored for synovitis, osteitis, tenosynovitis and periarticular inflammation according to the PsAMRIS method. Patients with psoriasis additionally received complete clinical investigation, high-resolution peripheral quantitative CT for detecting erosions and enthesiophytes and were followed up for at least 1 year for the development of PsA.47% of patients with psoriasis showed at least one inflammatory lesion on MRI. Synovitis was the most prevalent inflammatory lesion (38%), while osteitis (11%), tenosynovitis (4%) and periarticular inflammation (4%) were less frequent. The mean (±SD) PsAMRIS synovitis score was 3.0±2.5 units. Enthesiophytes and bone erosions were not different between patients with psoriasis with or without inflammatory MRI changes. The risk for developing PsA was as high as 60% if patients had subclinical synovitis and symptoms related to arthralgia, but only 13% if patients had normal MRIs and did not report arthralgia.Prevalence of subclinical inflammatory lesions is high in patients with cutaneous psoriasis. Arthralgia in conjunction with MRI synovitis constitutes a high-risk constellation for the development of PsA.
EVALuna2:13265

SUBJECTIVE ASSESSMENT OF PHYSICAL FUNCTION DOES NOT SUFFICIENTLY EXPLAIN VARIANCE OF MEASURED HAND FUNCTION AND GRIP STRENGTH IN ARTHRITIS PATIENTS AND NON-ARTHRITIS CONTROLS - Liphardt, Anna-Maria; Tascilar, Koray; Coppers, Birte; Manger, Eva; Liehr, Sonja; Bieniek, Lisa Maria; Bayat, Sara; Simon, David; Sticherling, Michael; Rech, Jürgen; Hueber, A.; Schett, Georg; et al. (ANNALS OF THE RHEUMATIC DISEASES, 2022)
CRIS-Team WoS Importer:2022-11-04

Subsets of CD1c+ DCs: Dendritic Cell Versus Monocyte Lineage - Heger, Lukas; Hofer, Thomas P.; Bigley, Venetia; de Vries, I. Jolanda M.; Dalod, Marc; Dudziak, Diana; Ziegler-Heitbrock, Loems (Frontiers in Immunology, 2020)
Currently three bona fide dendritic cell (DC) types are distinguished in human blood. Herein we focus on type 2 DCs (DC2s) and compare the three defining markers CD1c, CD172, and CD301. When using CD1c to define DC2s, a CD14+ and a CD14− subset can be detected. The CD14+ subset shares features with monocytes, and this includes substantially higher expression levels for CD64, CD115, CD163, and S100A8/9. We review the current knowledge of these CD1c+CD14+ cells as compared to the CD1c+CD14− cells with respect to phenotype, function, transcriptomics, and ontogeny. Here, we discuss informative mutations, which suggest that two populations have different developmental requirements. In addition, we cover subsets of CD11c+CD8− DC2s in the mouse, where CLEC12A+ESAMlow cells, as compared to the CLEC12A−ESAMhigh subset, also express higher levels of monocyte-associated markers CD14, CD3, and CD115. Finally, we summarize, for both man and mouse, the data on lower antigen presentation and higher cytokine production in the monocyte-marker expressing DC2 subset, which demonstrate that the DC2 subsets are also functionally distinct.
CRIS-Team Scopus Importer:2020-10-30
Keywords: CD14; CD172; CD1c; CD301; DC subsets; DC2; dendritic cells

Successful Treatment of a primary cutaneous aggressive epidermotropic CD8+T-cell Lymphoma with Nivolumab - Toussaint, Frédéric; Erdmann, M.; Grosch, Ella; Schuler, Gerold; Schliep, S.; Heinzerling, Lucie (JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, 2019)
CRIS-Team WoS Importer:2019-09-13

Successful treatment of refractory palmoplantar psoriasis in a psoriatic arthritis patient with the JAK inhibitor tofacitinib - Valor-Mendez, Larissa; Sticherling, Michael; Kleyer, Arnd; Schett, Georg (Clinical and Experimental Rheumatology, 2021)
CRIS-Team WoS Importer:2021-03-26

Successful treatment of ulcerative necrobiosis lipoidica with JAK inhibitor - Erfurt-Berge, Cornelia; Sticherling, Michael (Journal of the European Academy of Dermatology and Venereology, 2020)
Necrobiosis lipoidica (NL) is a rare granulomatous disease that predominantly affects middle aged women and is often associated with diabetes mellitus and other metabolic disorders 1 . About 30 % of the patients develop ulcerations within NL lesions on the lower leg, which complicate the course of disease and are often recalcitrant to standard wound care procedures 2 . Systemic therapies for NL are reported only for single cases or in small case series with varying outcome 3 . Randomized controlled trials are missing due to the character of NL as an orphan disease.
EVALuna2:212858

Sudden Otovestibular Dysfunction in 3 Metastatic Melanoma Patients Treated With Immune Checkpoint Inhibitors - Stuermer, Suzan H.; Lechner, Axel; Berking, Carola (Journal of Immunotherapy, 2021)
Immune-related adverse events have been described in 86%-96% of high-risk melanoma patients treated with immune checkpoint inhibitors (ICI), while in 17%-59% of cases these are classified as severe or even life-threatening. The most common immune-related adverse events include diarrhea, fatigue, hypothyroidism, and hepatitis. Bilateral uveitis and unspecific vertigo have been described in 1% of cases, respectively, in the pivotal studies of ICIs, but the affection of the vestibule-cochlear system has not been reported before. In this case series, we present 3-stage IV melanoma patients with sudden onset of otovestibular dysfunction (hearing loss and vestibulopathy), partly combined with uveitis because of ICIs. We describe detailed diagnostic work-up and therapeutic interventions and discuss possible pathogenic mechanisms of this rare and disabling event.
CRIS-Team WoS Importer:2021-06-11

Sun protection in outdoor workers – Development and validation of standardized questionnaires for behavior and knowledge - Rönsch, Henriette; Rocholl, Marc; Ludewig, Michaela; Staudt, Andreas; Langner, Mathias; Steeb, Theresa; Wilke, Annika; John, Swen Malte; Berking, Carola; Beissert, Stefan; Bauer, Andrea (Journal der Deutschen Dermatologischen Gesellschaft, 2024)
Background and objectives: Outdoor workers are at increased risk of developing non-melanoma skin cancer. We aimed to address the lack of validated German-language measurement instruments for outdoor workers’ sun safety behavior and knowledge by compiling and validating two questionnaires. Participants and methods: By expert consensus, items for the assessment of protective behavior (OccuSun) were compiled based on existing instruments. For knowledge, a translation of the Skin Cancer and Sun Knowledge (SCSK) scale was selected. After a pre-test, a validation study including 68 outdoor workers (62% female) was conducted in 2020. Results: The retest reliability was r = 0.93 (95% confidence interval: 0.86–0.96) for the protection score and rs = 0.78 (0.67–0.86) for the knowledge score. Protective behaviors were correlated with respective diary data (0.38 ≤ rs ≤ 0.74, p < 0.001) and skin pigmentation changes (–0.23 ≥ rs ≥ –0.42, 0.007 ≤ p ≤ 0.165) but not with self-reported sunburn frequency (0.21 ≥ rs ≥ –0.04). Conclusions: Among German outdoor workers, two questionnaires for the assessment of sun protection behavior (OccuSun) and knowledge (SCSK) demonstrated good reliability. The OccuSun had generally good validity. Both instruments are fit for subsequent validation to determine their sensitivity to change.
CRIS-Team Scopus Importer:2024-04-12

Suppression of proatherogenic leukocyte interactions by MCS-18 - Impact on advanced atherosclerosis in ApoE-deficient mice - Kühn, Constanze; Tauchi, Miyuki; Stumpf, Christian; Daniel, Christoph; Bäuerle, Tobias; Schwarz, Marc; Kerek, Franz; Steinkasserer, Alexander; Zinser, Elisabeth; Achenbach, Stephan; Dietel, Barbara (Atherosclerosis, 2016)
Atherosclerosis is associated with chronic inflammatory responses of the arterial blood vessels. The previously observed protective effect of the MCS-18 substance against the initiation of atherosclerosis in a murine model was explained by its pronounced anti-inflammatory activity. Here, we investigated its impact on murine plaque progression in advanced atherosclerosis and on proatherogenic processes.ApoE-deficient mice were fed a high-fat diet for 12 weeks to induce atherosclerosis, followed by normal chow and intraperitoneal injections of either MCS-18 (500 ?g, n = 10) or saline (n = 10) twice a week for another 12 weeks. Plaque size was reduced in MCS-18 treated mice compared to controls (p = 0.001), which was associated with a reduced size of the lipid core (p = 0.01). There was a decrease in apoptotic cells (p = 0.02), endothelial ICAM-1 expression (p < 0.001), and macrophage density (p = 0.01) in the MCS-18 group. In addition, human and murine dendritic cells (DCs) and human umbilical vein endothelial cells (HUVECs) were treated with MCS-18 (50-200 ?g/ml) to analyze cell migration and adhesion under flow conditions. MCS-18 reduced human (p = 0.01) and murine (p = 0.006) DC migration. Furthermore, adhesion of MCS-18-treated DCs to a HUVEC monolayer was decreased (p < 0.001). Compared to controls, CD209 (p < 0.001) and CCR7 (p = 0.003) expression was decreased in MCS-18-treated DCs, while in HUVECs lower levels of ICAM-1 (p < 0.001) and of phosphorylated NF-?B-p65 (p = 0.002) were observed. Blocking of ICAM-1 reduced DC adhesion (p < 0.001).MCS-18 exhibits interesting therapeutic effects when applied in advanced murine atherosclerosis. Its antiatherogenic impact might be associated with a suppressed adhesion to the endothelium due to down-regulation of endothelial ICAM-1 expression.
EVALuna2:12031

Surveillance of patients with conjunctival melanoma in German-speaking countries: A multinational survey of the German dermatologic cooperative oncology group - Wessely, Anja; Steeb, Theresa; Berking, Carola; Schlaak, Max; Heppt, Markus; Alter, Mareike; Bayerl, Christiane; Bender, Armin; Bruning, Guido; Dabrowski, Evelyn; Debus, Dirk; Devereux, Nina; et al. (European Journal of Cancer, 2021)
CRIS-Team Scopus Importer:2020-12-11

Survival of metastatic melanoma patients after dendritic cell vaccination correlates with expression of leukocyte phosphatidylethanolamine-binding protein 1/Raf kinase inhibitory protein - Buschow, Sonja I.; Ramazzotti, Matteo; Reinieren-Beeren, Inge M. J.; Heinzerling, Lucie; Westdorp, Harm; Stefanini, Irene; Beltrame, Luca; Hato, Stanleyson V.; Ellebaek, Eva; Gross, Stefanie; Van Anh Nguyen,; Weinlich, Georg; et al. (Oncotarget, 2017)
Immunotherapy for metastatic melanoma offers great promise but, to date, only a subset of patients have responded. There is an urgent need to identify ways of allocating patients to the most beneficial therapy, to increase survival and decrease therapy-associated morbidity and costs. Blood-based biomarkers are of particular interest because of their straightforward implementation in routine clinical care. We sought to identify markers for dendritic cell (DC) vaccine-based immunotherapy against metastatic melanoma through gene expression analysis of peripheral blood mononuclear cells. A large-scale microarray analysis of 74 samples from two treatment centers, taken directly after the first round of DC vaccination, was performed. We found that phosphatidylethanolamine binding protein 1 (PEBP1)/Raf Kinase inhibitory protein (RKIP) expression can be used to identify a significant proportion of patients who performed poorly after DC vaccination. This result was validated by q-PCR analysis on blood samples from a second cohort of 95 patients treated with DC vaccination in four different centers. We conclude that low PEBP1 expression correlates with poor overall survival after DC vaccination. Intriguingly, this was only the case for expression of PEBP1 after, but not prior to, DC vaccination. Moreover, the change in PEBP1 expression upon vaccination correlated well with survival. Further analyses revealed that PEBP1 expression positively correlated with genes involved in T cell responses but inversely correlated with genes associated with myeloid cells and aberrant inflammation including STAT3, NOTCH1, and MAPK1. Concordantly, PEBP1 inversely correlated with the myeloid/lymphoid-ratio and was suppressed in patients suffering from chronic inflammatory disease.
EVALuna2:34315

Survivin-specific T-cell reactivity correlates with tumor response and patient survival: A phase-II peptide vaccination trial in metastatic melanoma - Becker, Juergen C.; Andersen, Mads H.; Hofmeister-Mueller, Valeska; Wobser, Marion; Frey, Lidia; Sandig, Christiane; Walter, Steffen; Singh-Jasuja, Harpreet; Kämpgen, Eckhart; Opitz, Andreas; Zapatka, Marc; Broecker, Eva-B.; et al. (Cancer Immunology, Immunotherapy, 2012)
Keywords: Melanoma; Peptide vaccination; Survivin; T-cell reactivity; Therapy

Susceptibility of Melanoma Cells to Targeted Therapy Correlates with Protection by Blood Neutrophils - Wendlinger, Simone; Wohlfarth, Jonas; Siedel, Claudia; Kreft, Sophia; Kilian, Teresa; Junker, Sarah; Schmid, Luisa; Sinnberg, Tobias; Dischinger, Ulrich; Heppt, Markus; Wistuba-Hamprecht, Kilian; Meier, Friedegund; et al. (Cancers, 2024)
Elevated levels of peripheral blood and tumor tissue neutrophils are associated with poorer clinical response and therapy resistance in melanoma. The underlying mechanism and the role of neutrophils in targeted therapy is still not fully understood. Serum samples of patients with advanced melanoma were collected and neutrophil-associated serum markers were measured and correlated with response to targeted therapy. Blood neutrophils from healthy donors and patients with advanced melanoma were isolated, and their phenotypes, as well as their in vitro functions, were compared. In vitro functional tests were conducted through nonadherent cocultures with melanoma cells. Protection of melanoma cell lines by neutrophils was assessed under MAPK inhibition. Blood neutrophils from advanced melanoma patients exhibited lower CD16 expression compared to healthy donors. In vitro, both healthy-donor- and patient-derived neutrophils prevented melanoma cell apoptosis upon dual MAPK inhibition. The effect depended on cell–cell contact and melanoma cell susceptibility to treatment. Interference with protease activity of neutrophils prevented melanoma cell protection during treatment in cocultures. The negative correlation between neutrophils and melanoma outcomes seems to be linked to a protumoral function of neutrophils. In vitro, neutrophils exert a direct protective effect on melanoma cells during dual MAPK inhibition. This study further hints at a crucial role of neutrophil-related protease activity in protection.
CRIS-Team Scopus Importer:2024-05-24
Keywords: MAPK inhibition; melanoma; neutrophils; resistance

Sustainable responses in metastatic melanoma patients with and without brain metastases after elective discontinuation of anti-PD1-based immunotherapy due to complete response - Dimitriou, Florentia; Zaremba, Anne; Allayous, Clara; Kähler, Katharina C.; Gerard, Camille L.; Festino, Lucia; Schäfer, Sarah; Toussaint, Frédéric; Heinzerling, Lucie; Hassel, Jessica C.; Ascierto, Paolo A.; Michielin, Olivier; et al. (European Journal of Cancer, 2021)
Background: Anti-PD1–based immunotherapy is currently used in most patients with advanced melanoma. Despite the remarkable data regarding overall survival, the optimal treatment duration is still unknown. Methods: We evaluated the outcome of 125 patients with advanced melanoma with and without brain metastases (MBM), treated either with anti-PD1 monotherapy (N = 97) or combined with anti-CTLA4 (N = 28) after elective treatment discontinuation due to complete response (CR) (group A, N = 86), or treatment-limiting toxicity (N = 33) and investigator's decision (ID, N = 6) (group B) with subsequent CR. Results: For group A, median duration of treatment (mDoT) was 22 months (range 5–49) and median time to CR 9 months (range 2–47). Accordingly, mDoT for group B was 3 months (range 0–36) and median time to CR 7 months (range 1–32). Seven patients from group A and three from group B experienced disease recurrence. Off-treatment survival was not reached. Median off-treatment response time (mOTRt) was 19 months (range 0–42) and 25 months (range 0–66), respectively. For MBM, mOTRt was 17 months (range 7–41) and 28 months (range 9–39), respectively. After a median follow-up of 38 months (range 9–70), seven (5.6%) patients had deceased, one (0.8%) due to melanoma. Conclusions: Treatment discontinuation is feasible also in patients with MBM. Efficacy outcomes seemed to be similar in both groups of patients who achieved CR, regardless of reason for discontinuation. In patients who experienced disease relapse, treatment re-challenge with anti-PD1 resulted in subsequent renewed response.
CRIS-Team Scopus Importer:2021-04-16
Keywords: Anti-PD1 treatment; Brain metastases; Discontinuation; Immunotherapy; Melanoma

Sweet SIGNs: IgG glycosylation leads the way in IVIG-mediated resolution of inflammation - Brückner, Christin; Lehmann, Christian; Dudziak, Diana; Nimmerjahn, Falk (International Immunology, 2017)
A hallmark of many chronic inflammatory and autoimmune diseases is that there is an impaired resolution of inflammation and return to the steady state. The infusion of high doses of pooled serum IgG preparations from thousands of donors [intravenous immunoglobulin (IVIG) therapy] has been shown to induce resolution of inflammation in a variety of chronic inflammatory and autoimmune diseases, suggesting that IgG molecules can instruct the immune system to stop inflammatory processes and initiate the return to the steady state. The aim of this review is to discuss how insights into the mechanism of IVIG activity may help to understand the molecular and cellular pathways underlying resolution of inflammation. We will put a special emphasis on pathways dependent on the IgG FC domain and IgG sialylation, as several recent studies have provided new insights into how this glycosylation-dependent pathway modulates innate and adaptive immune responses through different sets of C-type or I-type lectins.
EVALuna2:34371

Systematic symptom screening in patients with advanced cancer treated in certified oncology centers: results of the prospective multicenter German KeSBa project - Braulke, Friederike; Para, Servet; Alt-Epping, Bernd; Tewes, Mitra; Bäumer, Markus; Haberland, Birgit; Mayer-Steinacker, Regine; Hopprich, Anne; de Wit, Maike; Grabe, Michaela; Bender-Säbelkampf, Sophia; Weßling, Caroline; et al. (Journal of Cancer Research and Clinical Oncology, 2023)
Purpose: Guidelines recommend a structured symptom screening (SC) for especially advanced cancer patients (CPs). The aim of this multicenter German prospective quality assurance project KeSBa (Kennzahl Symptom- und Belastungserfassung) was to gain knowledge on SC procedures in Oncology Centers (OCs) for advanced cancer patients and a first impression on the consequences of SC. Methods: The KeSBa project consisted of three phases: pilot, 3 months screening and feedback phase. Participating OCs decided to use either the Minimal Documentation System (MIDOS) or the Integrated Palliative care Outcome Scale (IPOS) and defined the cutoff values for positive screening results. Results: Out of 172 certified German OCs, 40 (23%) participated in the KeSBa pilot phase, 29 (16.8%) in the 3 months screening phase using MIDOS (n = 18, 58.6%) or IPOS (n = 11, 41.3%) and in the feedback round. 25/29 performed paper-based screening (86.2%). 2.963 CPs were screened. Results were documented for 1255 (42.2%, SC +) positive and 874 (29.5%, SC–) negative screenings depending on the center´s schedules: 452 SC + CPs (28.4%) and 42 SC– CPs (2.6%) had contact to specialized palliative care or other supportive specialist teams afterwards, 458 SC + CPs (28.8%) and 605 SC– CPs (38.1%) remained in standard oncology care. In the feedback round missing resources (personal and IT) and improved communication were mentioned most often. Conclusion: Routine SC is feasible in advanced CPs treated in OCs but associated with considerable workload. In 42.2% of CPs SC was classified as positive, indicating the need of further diagnostics or professional judgment. SC requires staff and IT resources.
CRIS-Team Scopus Importer:2023-05-19
Keywords: Cancer; IPOS; MIDOS; Palliative; Screening; Supportive

Systemic sclerosis - the dermatological perspective - Sticherling, Michael (Journal der Deutschen Dermatologischen Gesellschaft, 2019)
Systemic scleroderma/systemic sclerosis (SSc) is an inflammatory connective tissue disease clinically characterized by two major subtypes: limited and diffuse SSc. While both conditions present with Raynaud's phenomenon (paroxysmal digital ischemia), diffuse SSc is associated with rapid disease progression and early - prognostically relevant - involvement of internal organs. Treatment is challenging. In addition to general lifestyle modifications, measures include treatments aimed at improving circulation as well as immunosuppressive and immunomodulatory drugs. However, these agents are effective only in terms of slowing disease progression.
CRIS-Team WoS Importer:2019-08-13

Systemic therapy with calcitonin has positive clinical effects on systemic sclerosis in patients with cutaneous manifestations - Uslu, Ugur; Streiff, Laura; Sticherling, Michael (European Journal of Dermatology, 2018)
BACKGROUND: Calcitonin gene-related peptide (CGRP) is a vasodilatory neuropeptide that plays an important role in the blood vessels of heart and peripheral circulation, a lack of which may cause vasculopathies. OBJECTIVE: In this study, the clinical course of disease, as well as the efficacy, side effects, and patient satisfaction of systemic calcitonin therapy in patients with systemic sclerosis (SSc), was evaluated. METHODS: Forty-nine patients received repetitive intravenous calcitonin infusions as first-line treatment. The average number of cycles was 12.2 ± 10.3 over a period of 30 months (each cycle: 100 U/day over 10 days). Clinical examinations, laboratory tests, and organ imaging were performed before the start of, and at regular intervals during therapy in order to evaluate organ manifestations and the clinical course of the disease. In addition, patients' own experiences of the therapy, side effects, and therapy success were evaluated with standardized questionnaires. RESULTS: Over the course of the treatment, seven patients experienced improvements in their condition with a considerable reduction in digital ulceration and improved movement (14.3%). Pulmonary function in seven patients improved during the therapy (14.3%). With regards to side effects, nausea (41.7%), headaches (33.3%), fluctuations in blood pressure (29.2%), and flushing (29.2%) were observed. Overall, 45.8% of patients evaluated the therapy as good and 58.3% would undergo further courses of therapy with calcitonin. CONCLUSIONS: Systemic calcitonin treatment seems to have positive clinical effects on SSc and contributes to relieving symptoms, especially in patients with cutaneous manifestations. No severe side effects were reported during this study.
EVALuna2:34793

Systemic treatment of allergies Systemtherapie bei allergologischen Erkrankungen - Staubach, Petra; Ghoreishi, Yalda; Wagner, Nicola (Die Dermatologie, 2025)
Allergic rhinokonjunctivitis or asthma bronchiale and urticaria with or without angioedema are the most prevalent allergic diseases in childhood. Symptomatic relief can be achieved with antihistamines, corticosteroids and partially with the anti-immunoglobulin E (IgE) antibody omalizumab. Bradykinin-dependent angioedema, especially in childhood as the primary manifestation of hereditary angioedema (HAE), has to be ruled out as a differential diagnosis of histamine-induced angioedema. For HAE different therapy options in acute attacks and long-term prophylaxis are available. Timely initiation of specific immunotherapy for IgE-mediated allergy to aeroallergens, sublingually or subcutaneously (SCIT) applied, should be considered. Insect venom allergy can be treated with SCIT. Diagnosis of eosinophilic esophagitis is often delayed. Bolus events may be indicative of the disease. Elimination diets, proton pump inhibitors, topical corticosteroids and dupilumab may be used.
CRIS-Team Scopus Importer:2025-04-01
Keywords: Allergy; Angioedema; Eosinophilic esophagitis; Mast cell-mediated diseases; Pediatric systemic therapy

Systemic treatments in pediatric and adolescent dermatology Systemtherapien bei Kindern und Jugendlichen in der Dermatologie - Sticherling, Michael; Süßmuth, Kira (Die Dermatologie, 2025)
CRIS-Team Scopus Importer:2025-04-11

Systemische Sklerodermie - die dermatologische Sicht - Sticherling, Michael (Journal der Deutschen Dermatologischen Gesellschaft, 2019)
EVALuna2:212837

Systemische Therapien des Ulcus cruris - Dissemond, Joachim; Goerge, Tobias; Kroeger, Knut; Funke-Lorenz, Carolin; Reich-Schupke, Stefanie; Erfurt-Berge, Cornelia (Journal der Deutschen Dermatologischen Gesellschaft, 2018)
Successful management of patients with leg ulcers requires identification of the underlying etiology, with subsequent initiation of causal treatment, if feasible. Supplementary measures of first choice include stage-adjusted wound treatment, usually combined with compression therapy. The significance of systemic drugs has been the subject of controversial debate, depending on the underlying cause of the condition. The present review article is therefore meant to highlight current aspects of systemic drug therapies for the treatment of leg ulcers associated with chronic venous insufficiency, peripheral arterial disease, livedoid vasculopathy, vasculitis, necrobiosis lipoidica, calciphylaxis and pyoderma gangrenosum. In summary, the majority of therapeutic options presented herein are used off-label. While systemic drugs are promising options for the more common types of wounds such as venous, mixed or arterial leg ulcers, they do not represent the current standard of treatment. By contrast, systemic agents play a key role in the management of many of the other disorders presented herein. These agents primarily include immunomodulatory and rheological drugs used to expedite wound healing.
EVALuna2:34788

Systems biology-based investigation of cooperating microRNAs as monotherapy or adjuvant therapy in cancer - Lai, Xin; Eberhardt, Martin; Schmitz, Ulf; Vera, Julio (Nucleic Acids Research, 2019)
MicroRNAs (miRNAs) are short, noncoding RNAs that regulate gene expression by suppressing mRNA translation and reducing mRNA stability. A miRNA can potentially bind many mRNAs, thereby affecting the expression of oncogenes and tumor suppressor genes as well as the activity of whole pathways. The promise of miRNA therapeutics in cancer is to harness this evolutionarily conserved mechanism for the coordinated regulation of gene expression, and thus restoring a normal cell phenotype. However, the promiscuous binding of miRNAs can provoke unwanted off-target effects, which are usually caused by high-dose single-miRNA treatments. Thus, it is desirable to develop miRNA therapeutics with increased specificity and efficacy. To achieve that, we propose the concept of miRNA cooperativity in order to exert synergistic repression on target genes, thus lowering the required total amount of miRNAs. We first review miRNA therapies in clinical application. Next, we summarize the knowledge on the molecular mechanism and biological function of miRNA cooperativity and discuss its application in cancer therapies. We then propose and discuss a systems biology approach to investigate miRNA cooperativity for the clinical setting. Altogether, we point out the potential of miRNA cooperativity to reduce off-target effects and to complement conventional, targeted, or immune-based therapies for cancer.
CRIS-Team Scopus Importer:2019-09-17

Systems Immunology Approaches for Understanding of Primary Dendritic Cell Subpopulations in the Past, Present and Future - Heger, Lukas; Amon, Lukas; Lehmann, Christian; Dudziak, Diana (Elsevier, 2020)
Since their discovery in the 1970s, Dendritic cells (DCs) emerged as central regulators of immune responses controlling the induction and type of T cell immunity. There, DCs orchestrate the delicate balance of inducing protective immune responses against pathogens and tumors, while maintaining tolerance to self. Owing to their low abundance, short life, sensitivity and diversity, researchers had a hard time to dissect and identify specialized DC subsets in mice and men, track their ontogenetic origin and characterize key phenotypic and functional features utilizable for future therapeutic approaches. Thus, the DC community had to empower every technical innovation over the last decades as soon as possible. These advances range from the development of isolation and enrichment protocols to the generation of DC specific antibodies, early subtraction cDNA library screenings, bulk RNA sequencing and microarrays, simple flow cytometry and cell sorting to multicolor flow- and mass cytometry and unbiased -omics studies including analysis of the epigenome, transcriptome, lipidome and proteome. Within this review, we aim to briefly summarize the history of dendritic cell research ranging from their discovery to the onset of cutting-edge techniques with focus on unbiased single cell based approaches currently revolutionizing our understanding of DC biology.
CRIS-Team Scopus Importer:2024-12-16
Keywords: Affymetrix array; Agilent array; cDC1; cDC2; Conventional; Genearray; Genespring; Human; Illumina; Microarray; Ontogeny; pDC; Progeny; RNA-seq; scRNAseq; SPADE; Subtraction library; Transcription factor; tSNE; UMAP

Targeted label-free quantification of interleukin-8 in PMA-activated U937 cell secretome by nanoLC-ESI-MS/MS-sSRM. - Emirbayer, Pelin Esma; Gerer, Kerstin; Hoyer, Stefanie; Pischetsrieder, Monika (Proteomics, 2017)
Monocytes are a part of the innate immune system. Their differentiation into macrophages changes their cellular proteome and secretome. Particularly secretome components such as cytokines are crucial for immune response and inflammation in many diseases. Differentiation of human lymphoma cell line U937 can be triggered by phorbol 12-myristate 13-acetate (PMA). Screening of the cytokine release in U937 upon PMA stimulation by cytometric bead array almost exclusively showed interleukin-8. Next, a label-free nanoLC-ESI-MS/MS-sSRM method for quantification of interleukin-8 in the cell secretome was established and applied to monitor the time kinetics of PMA treatment in different concentrations. Targeted secretome analysis was achieved by scheduled SRM-MS using one proteotypic peptide as precursor ion and four mass transitions. Label-free quantification was performed by external calibration using interleukin-8 standard. Validation results indicated that the method was suited for the quantification of interleukin-8 in the secretome. The maximal interleukin-8 release of 62.4 ng/mL was observed after incubating cells treated by 50 ng/mL PMA for 48 h. The method can now be used for quantification of interleukin-8 release from different cells under various conditions. Furthermore, it can be easily expanded to other secreted proteins detected by untargeted screening methods. This article is protected by copyright. All rights reserve

Targeting Immune Cell Trafficking – Insights From Research Models and Implications for Future IBD Therapy - Wiendl, Maximilian; Becker, Elisabeth; Müller, Tanja; Voskens, Caroline; Neurath, Markus; Zundler, Sebastian (Frontiers in Immunology, 2021)
Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC) are multifactorial diseases with still unknown aetiology and an increasing prevalence and incidence worldwide. Despite plentiful therapeutic options for IBDs, the lack or loss of response in certain patients demands the development of further treatments to tackle this unmet medical need. In recent years, the success of the anti-α4β7 antibody vedolizumab highlighted the potential of targeting the homing of immune cells, which is now an important pillar of IBD therapy. Due to its complexity, leukocyte trafficking and the involved molecules offer a largely untapped resource for a plethora of potential therapeutic interventions. In this review, we aim to summarise current and future directions of specifically interfering with immune cell trafficking. We will comment on concepts of homing, retention and recirculation and particularly focus on the role of tissue-derived chemokines. Moreover, we will give an overview of the mode of action of drugs currently in use or still in the pipeline, highlighting their mechanisms and potential to reduce disease burden.
CRIS-Team Scopus Importer:2021-06-04
Keywords: homing; IBD; retention; T cell; therapy; trafficking

Targeting of DEC-205 on human dendritic cells results in efficient MHC class II-restricted antigen presentation - Birkholz, Katrin; Schwenkert, Michael; Kellner, Christian; Gross, Stefanie; Fey, Georg; Schuler-Thurner, Beatrice; Schuler, Gerold; Schaft, Niels; Dörrie, Jan (Blood, 2010)
The use of dendritic cells (DCs) in therapeutic cancer vaccination requires their loading with tumor-specific antigen(s). DEC-205, a phagocytosis receptor mediating antigen uptake, is associated with CD8+ T-cell responses in mice. Here we fused an anti-DEC-205scFv to an HLA-DP4-restricted epitope from the tumor antigen MAGE-A3, and examined the suitability and efficacy of DEC-205 to deliver a helper epitope to human monocytederived DCs (moDCs). The construct specifically bound DEC-205 on human moDCs without negative impact on DC phenotype and function. We measured antigen presentation with specific autologous CD4+ T cells, generated by TCR-RNA transfection. DEC-205 targeting resulted in significant major histocompatibility complex class II-restricted antigen presentation, and was superior to loading DCs by electroporation of mRNA encoding endosome-targeted MAGE-A3-DCLAMP or by direct peptide pulsing. Anti-DEC-205scFv-MAGE-A3 was presented 100 times more efficiently than the control constructs. DC maturation before or during incubation with anti-DEC-205scFv-MAGE-A3 reduced the interleukin-10/interleukin- 2 ratio. Moreover, we successfully applied the DEC-205 targeting strategy to moDCs from malignant melanoma patients. Again, DEC-205-targeted mature DCs (mDCs) presented the antigen more efficiently than peptide-pulsed DCs and maintained their stimulatory capacity after cryoconservation. Thus, DEC-205 targeting represents a feasible and effective method to deliver helper epitopes to DCs in anticancer vaccine strategies, which may also be suitable for DC targeting in vivo. © 2010 by The American Society of Hematology.
CRIS-Team Scopus Importer:2021-10-01

T Cell Costimulation Molecules CD80/86 Inhibit Osteoclast Differentiation by Inducing the IDO/Tryptophan Pathway - Bozec, Aline; Zaiss, Mario; Kagwiria, Rosebeth; Voll, Reinhard; Rauh, Manfred; Chen, Zhu; Müller-Schmucker, Sandra; Kroczek, Richard A.; Heinzerling, Lucie; Moser, Muriel; Mellor, Andrew L.; David, Jean-Pierre; et al. (Science Translational Medicine, 2014)
Bone resorption is seminal for the physiological remodeling of bone during life. However, this process needs to be strictly controlled; excessive bone resorption results in pathologic bone loss, osteoporosis, and fracture. We describe a control mechanism of bone resorption by the adaptive immune system. CD80/86, a pair of molecules expressed by antigen-presenting cells and involved in T cell costimulation, act as negative regulator for the generation of bone-resorbing osteoclasts. CD80/86-deficient mice were osteopenic because of increased osteoclast differentiation. CD80/86-deficient osteoclasts escaped physiological inhibition by CTLA-4 or regulatory T cells. Mechanistically, engagement of CD80/86 by CTLA-4 induced activation of the enzyme indoleamine 2,3-dioxygenase (IDO) in osteoclast precursors, which degraded tryptophan and promoted apoptosis. Concordantly, IDO-deficient mice also showed an osteopenic bone phenotype with higher numbers of osteoclast precursors and osteoclasts. Also, IDO-deficient mononuclear cells escaped the anti-osteoclastogenic effect of CTLA-4. This molecular mechanism was also present in humans because targeting CD80/86 by abatacept, a CTLA-4-immunoglobulin fusion protein, reduced, whereas blockade of CTLA-4 by ipilimumab antibody enhanced, the frequency of peripheral osteoclast precursors and osteoclastogenesis. In summary, these data show an important role of the adaptive immune system, in particular T cell CD80/86 costimulation molecules, in the physiological regulation of bone resorption and preservation of bone mass, as well as affect the understanding of the function of current and future drugs fostering or blocking the effects of CTLA-4 in humans.
EVALuna2:12912

T-cell receptor transfer for boosting HIV-1-specific T-cell immunity in HIV-1-infected patients - Mummert, Christiane; Hofmann, Christian; Hueckelhoven, Angela G.; Bergmann, Silke; Mueller-Schmucker, Sandra M.; Harrer, Ellen G.; Dörrie, Jan; Schaft, Niels; Harrer, Thomas (Aids, 2016)
Strategies to cure HIV-1 infection require the eradication of viral reservoirs. An innovative approach for boosting the cytotoxic T-lymphocyte response is the transfer of T-cell receptors (TCRs). Previously, we have shown that electroporation of TCR-encoding mRNA is able to reprogram CD8 T cells derived from healthy donors. So far, it is unknown whether the transfer of HIV-1-specific TCRs is capable to reprogram CD8 T cells of HIV-1-infected patients. To assess the efficiency of TCR-transfer by mRNA electroporation and the functionality of reprogramed T cells in HIV-1-infected patients, we performed an in-vitro analysis of TCR-transfer into T cells from HIV-1-infected patients in various stages of disease and from healthy controls.Peripheral blood mononuclear cells from 16 HIV-1-infected patients (nine HLA-A02-positive, seven HLA-A02-negative) and from five healthy controls were electroporated with mRNA-constructs encoding TCRs specific for the HLA-A02/HIV-1-gag p17 epitope SLYNTVATL (SL9). Functionality of the TCRs was measured by ?IFN-ELISpot assays.SL9/TCR transfection into peripheral blood mononuclear cells from both HLA-A02-positive and HLA-A02-negative HIV-1-infected patients and from healthy blood donors reprogramed T cells for recognition of SL9-presenting HLA-A02-positive cells in ?IFN-ELISpot assays. SL9/TCR-transfer into T cells from an immunodeficient AIDS patient could induce recognition of SL9-expressing target cells only after reversion of T-cell dysfunction by antiretroviral therapy.The transfer of HIV-1-p17-specific TCRs into T cells is functional both in HIV-1-infected patients as well as in healthy blood donors. TCR-transfer is a promising method to boost the immune system against HIV-1.
EVALuna2:13288

T-cell responses in merkel cell carcinoma: Implications for improved immune checkpoint blockade and other therapeutic options - Gehrcken, Laura; Sauerer, Tatjana; Schaft, Niels; Dörrie, Jan (International Journal of Molecular Sciences, 2021)
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with rising incidence and high mortality. Approximately 80% of the cases are caused by the human Merkel cell polyomavirus, while the remaining 20% are induced by UV light leading to mutations. The standard treatment of metastatic MCC is the use of anti-PD-1/-PD-L1-immune checkpoint inhibitors (ICI) such as Pembrolizumab or Avelumab, which in comparison with conventional chemotherapy show better overall response rates and longer duration of responses in patients. Nevertheless, 50% of the patients do not respond or develop ICI-induced, immune-related adverse events (irAEs), due to diverse mechanisms, such as down-regulation of MHC complexes or the induction of anti-inflammatory cytokines. Other immunotherapeutic options such as cytokines and pro-inflammatory agents or the use of therapeutic vaccination offer great ameliorations to ICI. Cytotoxic T-cells play a major role in the effectiveness of ICI, and tumour-infiltrating CD8+ T-cells and their phenotype contribute to the clinical outcome. This literature review presents a summary of current and future checkpoint inhibitor therapies in MCC and demonstrates alternative therapeutic options. Moreover, the importance of T-cell responses and their beneficial role in MCC treatment is discussed.
CRIS-Team Scopus Importer:2021-08-20
Keywords: Immune checkpoint blockade; Immunotherapy; Large T antigen; Merkel cell carcinoma; Merkel cell polyomavirus; T-cell response; Tumour microenvironment; Tumour mutational burden

Tebentafusp als neuartige Immuntherapie zeigt einen Überlebensvorteil beim metastasierten Uveamelanom und wird bereits in Deutschland eingesetzt. - Hassel, Jessica C.; Berking, Carola (Journal der Deutschen Dermatologischen Gesellschaft, 2022)
EVALuna2:502114

Tebentafusp in Patients with Metastatic Uveal Melanoma: A Real-Life Retrospective Multicenter Study. - Tomsitz, Dirk; Ruf, Theresa; Heppt, Markus; Staeger, Ramon; Ramelyte, Egle; Dummer, Reinhard; Garzarolli, Marlene; Meier, Friedegund; Meier, Eileen; Richly, Heike; Gromke, Tanja; Siveke, Jens T.; et al. (Cancers, 2023)
BACKGROUND: Tebentafusp has recently been approved for the treatment of metastatic uveal melanoma (mUM) after proving to have survival benefits in a first-line setting. PATIENTS AND METHODS: This retrospective, multicenter study analyzed the outcomes and safety of tebentafusp therapy in 78 patients with mUM. RESULTS: Patients treated with tebentafusp had a median PFS of 3 months (95% CI 2.7 to 3.3) and a median OS of 22 months (95% CI 10.6 to 33.4). In contrast to a published Phase 3 study, our cohort had a higher rate of patients with elevated LDH (65.4% vs. 35.7%) and included patients with prior systemic and local ablative therapies. In patients treated with tebentafusp following ICI, there was a trend for a longer median OS (28 months, 95% CI 26.9 to 29.1) compared to the inverse treatment sequence (24 months, 95% CI 13.0 to 35.0, p = 0.257). The most common treatment-related adverse events were cytokine release syndrome in 71.2% and skin toxicity in 53.8% of patients. Tumor lysis syndrome occurred in one patient. CONCLUSIONS: Data from this real-life cohort showed a median PFS/OS similar to published Phase 3 trial data. Treatment with ICI followed by tebentafusp may result in longer PFS/OS compared to the inverse treatment sequence.
EVALuna2:538270

TEMPORAL MIGRATION OF IMMUNE CELLS FROM PSORIATIC SKIN TO JOINTS INITIATING SYNOVIAL INFLAMMATION IN PSORIATIC ARTHRITIS - Raimondo, Maria Gabriella; Rauber, Simon; Xu, Cong; Mohammadian, Hashem; Vogg, Mario; Anchang, Charles Gwellem; Rigau, Aleix; Luber, M.; Labinsky, Hannah; Soare, A.; Distler, Jörg; Fearon, U.; et al. (ANNALS OF THE RHEUMATIC DISEASES, 2022)
CRIS-Team WoS Importer:2022-11-04

Th17 Cell-Mediated Colitis Is Positively Regulated by Interferon Regulatory Factor 4 in a T Cell-Extrinsic Manner - Buchele, Vera; Konein, Patrick; Vogler, Tina; Kunert, Timo; Enderle, Karin; Khan, Hanif; Büttner-Herold, Maike; Lehmann, Christian; Amon, Lukas; Wirtz, Stefan; Dudziak, Diana; Neurath, Markus; et al. (Frontiers in Immunology, 2021)
Inflammatory bowel diseases (IBDs) are characterized by chronic, inflammatory gastrointestinal lesions and often require life-long treatment with immunosuppressants and repetitive surgical interventions. Despite progress in respect to the characterization of molecular mechanisms e.g. exerted by TNF-alpha, currently clinically approved therapeutics fail to provide long-term disease control for most patients. The transcription factor interferon regulatory factor 4 (IRF4) has been shown to play important developmental as well as functional roles within multiple immune cells. In the context of colitis, a T cell-intrinsic role of IRF4 in driving immune-mediated gut pathology is established. Here, we conversely addressed the impact of IRF4 inactivation in non-T cells on T cell driven colitis in vivo. Employing the CD4+CD25− naïve T cell transfer model, we found that T cells fail to elicit colitis in IRF4-deficient compared to IRF4-proficient Rag1−/− mice. Reduced colitis activity in the absence of IRF4 was accompanied by hampered T cell expansion both within the mesenteric lymph node (MLN) and colonic lamina propria (cLP). Furthermore, the influx of various myeloids, presumably inflammation-promoting cells was abrogated overall leading to a less disrupted intestinal barrier. Mechanistically, gene profiling experiments revealed a Th17 response dominated molecular expression signature in colon tissues of IRF4-proficient, colitic Rag1−/− but not in colitis-protected Rag1−/−Irf4−/− mice. Colitis mitigation in Rag1−/−Irf4−/− T cell recipients resulted in reduced frequencies and absolute numbers of IL-17a-producing T cell subsets in MLN and cLP possibly due to a regulation of conventional dendritic cell subset 2 (cDC2) known to impact Th17 differentiation. Together, extending the T cell-intrinsic role for IRF4 in the context of Th17 cell driven colitis, the provided data demonstrate a Th17-inducing and thereby colitis-promoting role of IRF4 through a T cell-extrinsic mechanism highlighting IRF4 as a putative molecular master switch among transcriptional regulators driving immune-mediated intestinal inflammation through both T cell-intrinsic and T cell-extrinsic mechanisms. Future studies need to further dissect IRF4 controlled pathways within distinct IRF4-expressing myeloid cell types, especially cDC2s, to elucidate the precise mechanisms accounting for hampered Th17 formation and, according to our data, the predominant mechanism of colitis protection in Rag1−/−Irf4−/− T cell receiving mice.
CRIS-Team Scopus Importer:2021-02-26
Keywords: inflammatory bowel disease (IBD); interferon regulatory factor 4 (IRF4); intestinal inflammation; myeloid cells; Th17

The acidic protein rich in leucines Anp32b is an immunomodulator of inflammation in mice - Chemnitz, Jan; Pieper, Dorothea; Stich, Lena; Schumacher, Udo; Balabanov, Stefan; Spohn, Michael; Grundhoff, Adam; Steinkasserer, Alexander; Hauber, Joachim; Zinser, Elisabeth (Scientific Reports, 2019)
ANP32B belongs to a family of evolutionary conserved acidic nuclear phosphoproteins (ANP32A-H). Family members have been described as multifunctional regulatory proteins and proto-oncogenic factors affecting embryonic development, cell proliferation, apoptosis, and gene expression at various levels. Involvement of ANP32B in multiple processes of cellular life is reflected by the previous finding that systemic gene knockout (KO) of Anp32b leads to embryonic lethality in mice. Here, we demonstrate that a conditional KO of Anp32b is well tolerated in adult animals. However, after immune activation splenocytes isolated from Anp32b KO mice showed a strong commitment towards Th17 immune responses. Therefore, we further analyzed the respective animals in vivo using an experimental autoimmune encephalomyelitis (EAE) model. Interestingly, an exacerbated clinical score was observed in the Anp32b KO mice. This was accompanied by the finding that animal-derived T lymphocytes were in a more activated state, and RNA sequencing analyses revealed hyperactivation of several T lymphocyte-associated immune modulatory pathways, attended by significant upregulation of Tfh cell numbers that altogether might explain the observed strong autoreactive processes. Therefore, Anp32b appears to fulfill a role in regulating adequate adaptive immune responses and, hence, may be involved in dysregulation of pathways leading to autoimmune disorders and/or immune deficiencies.
CRIS-Team WoS Importer:2019-04-02

The AP-1 Transcription Factor c-Jun Promotes Arthritis by Regulating Cyclooxygenase-2 and Arginase-1 Expression in Macrophages - Hannemann, Nicole; Jordan, Jutta; Paul, Sushmita; Reid, Stephen; Baenkler, Hanns-Wolf; Sonnewald, Sophia; Bäuerle, Tobias; Vera, Julio; Schett, Georg; Bozec, Aline (Journal of Immunology, 2017)
Activation of proinflammatory macrophages is associated with the inflammatory state of rheumatoid arthritis. Their polarization and activation are controlled by transcription factors such as NF-?B and the AP-1 transcription factor member c-Fos. Surprisingly, little is known about the role of the AP-1 transcription factor c-Jun in macrophage activation. In this study, we show that mRNA and protein levels of c-Jun are increased in macrophages following pro- or anti-inflammatory stimulations. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment cluster analyses of microarray data using wild-type and c-Jun-deleted macrophages highlight the central function of c-Jun in macrophages, in particular for immune responses, IL production, and hypoxia pathways. Mice deficient for c-Jun in macrophages show an amelioration of inflammation and bone destruction in the serum-induced arthritis model. In vivo and in vitro gene profiling, together with chromatin immunoprecipitation analysis of macrophages, revealed direct activation of the proinflammatory factor cyclooxygenase-2 and indirect inhibition of the anti-inflammatory factor arginase-1 by c-Jun. Thus, c-Jun regulates the activation state of macrophages and promotes arthritis via differentially regulating cyclooxygenase-2 and arginase-1 levels.
EVALuna2:13412

The Art of Making Moulages - a hidden Art? - Sticherling, Michael; Groenhardt, K.; Saake, Marc (JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, 2019)
CRIS-Team WoS Importer:2019-05-17

The CD83 Molecule – An Important Immune Checkpoint - Grosche, Linda; Knippertz, Ilka; König, Christina; Royzman, Dmytro; Wild, Andreas; Zinser, Elisabeth; Sticht, Heinrich; Muller, Yves; Steinkasserer, Alexander; Lechmann, Matthias (Frontiers in Immunology, 2020)
The CD83 molecule has been identified to be expressed on numerous activated immune cells, including B and T lymphocytes, monocytes, dendritic cells, microglia, and neutrophils. Both isoforms of CD83, the membrane-bound as well as its soluble form are topic of intensive research investigations. Several studies revealed that CD83 is not a typical co-stimulatory molecule, but rather plays a critical role in controlling and resolving immune responses. Moreover, CD83 is an essential factor during the differentiation of T and B lymphocytes, and the development and maintenance of tolerance. The identification of its interaction partners as well as signaling pathways have been an enigma for the last decades. Here, we report the latest data on the expression, structure, and the signaling partners of CD83. In addition, we review the regulatory functions of CD83, including its striking modulatory potential to maintain the balance between tolerance versus inflammation during homeostasis or pathologies. These immunomodulatory properties of CD83 emphasize its exceptional therapeutic potential, which has been documented in specific preclinical disease models.
CRIS-Team Scopus Importer:2020-05-08
Keywords: autoimmunity; CD83; immune tolerance; Treg cells; viral escape mechanism

The CD83 molecule expressed by dendritic cells is a checkpoint to regulate resolution of inflammation as well as homeostasis within periphery and CNS - Wild, Andreas; Krzyzak, Lena; Mattner, Jochen; Winkler, Thomas; Nitschke, Lars; Steinkasserer, Alexander (2018)
EVALuna2:36214

The COVID-19 pandemic: implications for patients undergoing immunomodulating or immunosuppressive treatments in dermatology - Reinholz, Markus; French, Lars E.; Berking, Carola; Heppt, Markus (European Journal of Dermatology, 2020)
CRIS-Team WoS Importer:2021-02-26

The current spectrum of contact sensitization in patients with chronic leg ulcers or stasis dermatitis - new data from the Information Network of Departments of Dermatology (IVDK) - Geier, Johannes; Mahler, Vera; Erfurt-Berge, Cornelia (Contact Dermatitis, 2017)
BACKGROUND: Patients with lower leg dermatitis, chronic venous insufficiency or chronic leg ulcers have a high prevalence of contact sensitization. OBJECTIVES: To identify the current spectrum of contact allergens in these patients. PATIENTS AND METHODS: Data of the Information Network of Departments of Dermatology on 5264 patients with the above diagnoses from the years 2003 to 2014 (study group) were compared with data on 4881 corresponding patients from 1994 to 2003 (historical control group) and with a current control group without these diagnoses (n = 55 510). RESULTS: Allergic contact dermatitis was diagnosed less frequently in the study group than in the historical control group (25.9% versus 16.9%; p < 0.001), and contact sensitization to most allergens had declined. The allergen spectrum, however, was largely unchanged. Important allergens are Myroxylon pereirae (balsam of Peru) (14.8% positive reactions), fragrance mix I (11.4%), lanolin alcohol (7.8%), colophonium (6.6%), neomycin sulfate (5.0%), cetearyl alcohol (4.4%), oil of turpentine (3.1%), and paraben mix (2.6%). Patch testing with additional series showed sensitization to Amerchol L-101 (9.7%), tert-butyl hydroquinone (8.7%), framycetin sulfate (5.0%), and gentamicin sulfate (3.1%). CONCLUSIONS: Topical preparations for treating the above-mentioned conditions should not contain fragrances, Myroxylon pereirae, and colophonium. The special allergen spectrum has to be considered in patch testing.
EVALuna2:35405

The Current State of Systemic Therapy of Metastatic Uveal Melanoma - Koch, Elias; Heppt, Markus; Berking, Carola (American Journal of Clinical Dermatology, 2024)
Uveal melanoma (UM) is genetically a distinct tumor compared to cutaneous melanoma (CM), and due to its low mutational burden, it is far less perceptible to the immune system. Thus, treatments that have revolutionized the treatment of CM remain widely inefficient in metastatic UM or only demonstrate effectiveness in a small subpopulation of patients. To this end, the therapeutic benefit of immune checkpoint blockade is very limited and may come at the expense of severe immune-related adverse events that could potentially affect all organ systems. Notably, tebentafusp, an entirely novel class of anti-cancer drugs, has received official authorization for the treatment of metastatic UM. It is the first agent that demonstrated a survival advantage in a randomized controlled trial of metastatic UM patients. Despite the survival benefit and approval, the restriction of tebentafusp to HLA-A*02:01-positive patients and the low objective response rate indicate the persistent need for additional therapies. Thus, liver-directed therapies are commonly used for tumor control of hepatic metastases and represent a central pillar of the daily management of liver-dominant disease. Further, promising data from targeted therapies independent of MEK-inhibitors, such as the combination of darovasertib and crizotinib, raise hope for additional options in metastatic UM in the future. This narrative review provides a timely and comprehensive overview of the current treatment landscape for metastatic UM.
CRIS-Team Scopus Importer:2024-06-28

The delivery of antigens to dendritic cells is a potent futureoption for anti-tumor therapies - Lehmann, Christian; Heger, Lukas; Neubert, K.; Harzer, Christina; Amon, Lukas; Yamazaki, S.; Heidkamp, Gordon Frederik; Eissing, N.; Krug, A.; Leusen, J.; Ravetch, J.; Nimmerjahn, Falk; et al. (2017)
EVALuna2:34372

The distribution of C-type lectin receptors in the Dendritic cell membrane - Lühr, Jennifer; Eissing, N.; Heidkamp, Gordon Frederik; Lehmann, C. H. K.; Heger, Lukas; Dudziak, Diana (2017)
EVALuna2:34370

The Effect of Hyperthermia and Radiotherapy Sequence on Cancer Cell Death and the Immune Phenotype of Breast Cancer Cells - Sengedorj, Azzaya; Hader, Michael; Heger, Lukas; Frey, Benjamin; Dudziak, Diana; Fietkau, Rainer; Ott, Oliver; Scheidegger, Stephan; Barba, Sergio Mingo; Gaipl, Udo; Rückert, Michael (Cancers, 2022)
Hyperthermia (HT) is an accepted treatment for recurrent breast cancer which locally heats the tumor to 39–44◦C, and it is a very potent sensitizer for radiotherapy (RT) and chemotherapy. However, currently little is known about how HT with a distinct temperature, and particularly, how the sequence of HT and RT changes the immune phenotype of breast cancer cells. Therefore, human MDA-MB-231 and MCF-7 breast cancer cells were treated with HT of different temperatures (39, 41 and 44◦C), alone and in combination with RT (2 × 5 Gy) in different sequences, with either RT or HT first, followed by the other. Tumor cell death forms and the expression of immune checkpoint molecules (ICMs) were analyzed by multicolor flow cytometry. Human monocyte-derived dendritic cells (moDCs) were differentiated and co-cultured with the treated cancer cells. In both cell lines, RT was the main stressor for cell death induction, with apoptosis being the prominent cell death form in MCF-7 cells and both apoptosis and necrosis in MDA-MB-231 cells. Here, the sequence of the combined treatments, either RT or HT, did not have a significant impact on the final outcome. The expression of all of the three examined immune suppressive ICMs, namely PD-L1, PD-L2 and HVEM, was significantly increased on MCF-7 cells 120 h after the treatment of RT with HT of any temperature. Of special interest for MDA-MB-231 cells is that only combinations of RT with HT of both 41 and 44◦C induced a significantly increased expression of PD-L2 at all examined time points (24, 48, 72, and 120 h). Generally, high dynamics of ICM expression can be observed after combined RT and HT treatments. There was no significant difference between the different sequences of treatments (either HT + RT or RT + HT) in case of the upregulation of ICMs. Furthermore, the co-culture of moDCs with tumor cells of any treatment had no impact on the expression of activation markers. We conclude that the sequence of HT and RT does not strongly affect the immune phenotype of breast cancer cells. However, when HT is combined with RT, it results in an increased expression of distinct immune suppressive ICMs that should be considered by including immune checkpoint inhibitors in multimodal tumor treatments with RT and HT. Further, combined RT and HT affects the immune system in the effector phase rather than in the priming phase.
CRIS-Team Scopus Importer:2022-04-29
Keywords: breast cancer; dendritic cell activation; hyperthermia; hyperthermia treatment sequence; immune checkpoint molecules; immune phenotype; radiotherapy

The effects of dexmedetomidine and tramadol on post-operative pain and agitation, and extubation quality in paediatric patients undergoing adenotonsillectomy surgery: A randomized trial - Koceroglu, Ikbal; Devrim, Sibel; Bingol Tanriverdi, Tugba; Gura Celik, Melek (Journal of Clinical Pharmacy and Therapeutics, 2019)
What is known and objective Adenotonsillectomies are common surgical procedures performed under general anaesthesia in childhood. Post-operative pain and agitation are complications associated with this procedure. We compared the effects of dexmedetomidine and tramadol on post-operative pain, agitation, haemodynamic parameters, and extubation quality in patients undergoing an adenotonsillectomy using sevoflurane as an anaesthetic agent. Methods Sixty paediatric patients who had undergone an adenotonsillectomy were included in this study. The patients were randomized into two groups that received either dexmedetomidine (n = 30) or tramadol (n = 30). Haemodynamic variables, extubation time, post-operative pain, agitation and adverse events were recorded for all patients. Post-operative pain was assessed with the pain point system scale (PPSS), and agitation was assessed using the Riker Sedation-Agitation Scale (SAS). Results Patients in the dexmedetomidine group had significantly lower heart rates than the tramadol group. In addition, patients in the dexmedetomidine group had significantly lower post-operative PPSS and Riker SAS scores than patients in the tramadol group. Not breathing, cough-bucking and desaturation after extubation occurred less frequently in patients who received dexmedetomidine than in patients who received tramadol. However, the time to extubation was significantly longer for patients who received dexmedetomidine. What is new and conclusion Our study demonstrated that dexmedetomidine was more effective than tramadol for mitigating post-operative pain and agitation in paediatric patients following an adenotonsillectomy with sevoflurane. Although dexmedetomidine was associated with a longer time to extubation, it was also associated with fewer complications following extubation compared with tramadol.
CRIS-Team WoS Importer:2019-12-13

The future of affordable cancer immunotherapy - Schaft, Niels; Dörrie, Jan; Schuler, Gerold; Schuler-Thurner, Beatrice; Sallam, Husam; Klein, Shiri; Eisenberg, Galit; Frankenburg, Shoshana; Lotem, Michal; Khatib, Areej (Frontiers in Immunology, 2023)
The treatment of cancer was revolutionized within the last two decades by utilizing the mechanism of the immune system against malignant tissue in so-called cancer immunotherapy. Two main developments boosted cancer immunotherapy: 1) the use of checkpoint inhibitors, which are characterized by a relatively high response rate mainly in solid tumors; however, at the cost of serious side effects, and 2) the use of chimeric antigen receptor (CAR)-T cells, which were shown to be very efficient in the treatment of hematologic malignancies, but failed to show high clinical effectiveness in solid tumors until now. In addition, active immunization against individual tumors is emerging, and the first products have reached clinical approval. These new treatment options are very cost-intensive and are not financially compensated by health insurance in many countries. Hence, strategies must be developed to make cancer immunotherapy affordable and to improve the cost-benefit ratio. In this review, we discuss the following strategies: 1) to leverage the antigenicity of “cold tumors” with affordable reagents, 2) to use microbiome-based products as markers or therapeutics, 3) to apply measures that make adoptive cell therapy (ACT) cheaper, e.g., the use of off-the-shelf products, 4) to use immunotherapies that offer cheaper platforms, such as RNA- or peptide-based vaccines and vaccines that use shared or common antigens instead of highly personal antigens, 5) to use a small set of predictive biomarkers instead of the “sequence everything” approach, and 6) to explore affordable immunohistochemistry markers that may direct individual therapies.
CRIS-Team Scopus Importer:2023-09-29
Keywords: adoptive cell therapy; affordable; biomarkers; immunohistochemistry; immunotherapy; microbiome; RNA-based vaccines

The Generation of CAR-Transfected Natural Killer T Cells for the Immunotherapy of Melanoma - Simon, Bianca; Wiesinger, Manuel; Maerz, Johannes; Wistuba-Hamprecht, Kilian; Weide, Benjamin; Schuler-Thurner, Beatrice; Schuler, Gerold; Dörrie, Jan; Uslu, Ugur (International Journal of Molecular Sciences, 2018)
Natural killer T (NKT) cells represent a cell subpopulation that combines characteristics of natural killer (NK) cells and T cells. Through their endogenous T-cell receptors (TCRs), they reveal a pronounced intrinsic anti-tumor activity. Thus, a NKT cell transfected with a chimeric antigen receptor (CAR), which recognizes a tumor-specific surface antigen, could attack tumor cells antigen-specifically via the CAR and additionally through its endogenous TCR. NKT cells were isolated from peripheral blood mononuclear cells (PBMCs), expanded, and electroporated with mRNA encoding a chondroitin sulfate proteoglycan 4 (CSPG4)-specific CAR. The CAR expression on NKT cells and their in vitro functionality were analyzed. A transfection efficiency of more than 80% was achieved. Upon stimulation with melanoma cells, CAR-NKT cells produced cytokines antigen-specifically. Compared with conventional CAR-T cells, cytokine secretion of CAR-NKT cells was generally lower. Specific cytotoxicity, however, was similar with CAR-NKT cells showing a trend towards improved cytotoxicity. Additionally, CAR-NKT cells could kill target cells through their endogenous TCRs. In summary, it is feasible to generate CAR-NKT cells by using mRNA electroporation. Their CAR-mediated cytotoxicity is at least equal to that of conventional CAR-T cells, while their intrinsic cytotoxic activity is maintained. Thus, CAR-NKT cells may represent a valuable alternative to conventional CAR-T cells for cancer immunotherapy.
EVALuna2:34785

The Generation of CAR-transfected NKT Cells for the Immunotherapy of Melanoma - Simon, B.; Wiesinger, M.; Marz, J.; Wistuba-Hamprecht, K.; Weide, B.; Schuler-Thurner, Beatrice; Schuler, Gerold; Dörrie, Jan; Uslu, Ugur (2018)
EVALuna2:34767

The genetic basis for most patients with pustular skin disease remains elusive - Mössner, R.; Wilsmann-Theis, D.; Oji, V.; Gkogkolou, P.; Löhr, S.; Schulz, P.; Körber, A.; Prinz, J. C.; Renner, R.; Schäkel, K.; Vogelsang, L.; Peters, K. P.; et al. (British Journal of Dermatology, 2017)
Rare variants in the genes IL36RN, CARD14 and AP1S3 have been identified to cause/ contribute to pustular skin diseases, primarily generalized pustular psoriasis (GPP).To better understand the disease-relevance of these genes, we screened our cohorts of patients with pustular skin diseases (primarily GPP and palmoplantar pustular psoriasis [PPP]) for coding changes in these three genes. Carriers of single heterozygous IL36RN mutations were screened for a second mutation in IL36RN.Coding exons of IL36RN, CARD14 and AP1S3 were sequenced in 67 patients - 61 with GPP, 2 with acute generalized exanthematous pustulosis and 4 with acrodermatitis continua suppurativa Hallopeau. We screened IL36RN and AP1S3 for intragenic copy-number-variants, 258 PPP patients for coding changes in AP1S3. 11 heterozygous IL36RN mutations carriers were analyzed for a 2(nd) non-coding IL36RN mutation. Genotype-phenotype-correlations in carriers/ non-carriers of IL36RN mutations were assessed within the GPP cohort.The majority of patients (GPP:64%) did not carry rare variants in any of the three genes. Bi-allelic and mono-allelic IL36RN mutations were identified in 15 and 5 GPP patients, respectively. Non-coding rare IL36RN variants were not identified in heterozygous carriers. The only significant genotype-phenotype-correlation observed for IL36RN mutation carriers was early age of disease onset. Additional rare CARD14 or AP1S3 variants were identified in 15% of IL36RN mutations carriers.The identification of IL36RN mutation carriers harboring additional rare variants in CARD14 or AP1S3, indicates a more complex mode of inheritance of pustular psoriasis. Our results suggest additional disease-causing genetic factors in heterozygous IL36RN mutation carriers outside IL36RN. This article is protected by copyright. All rights reserved.
EVALuna2:9330

THE GERMAN AD REGISTRY TREATGERMANY: RESULTS FROM AN INTERIM DATA ANALYSIS ON BASELINE CHARACTERISTICS, COMORBIDITIES AND TREATMENT HISTORY - Heratizadeh, Annice; Haufe, Eva; Stoelzl, Dora; Abraham, Susanne; Heinrich, Luise; Kleinheinz, Andreas; Wollenberg, Andreas; Weisshaar, Elke; Augustin, Matthias; Wiemers, Franca; Zink, Alexander; Von Kiedrowski, Ralph; et al. (ACTA DERMATO-VENEREOLOGICA, 2021)
CRIS-Team WoS Importer:2021-05-07

The global impact of the COVID-19 pandemic on the management and course of chronic urticaria - Kocaturk, Emek; Salman, Andac; Cherrez-Ojeda, Ivan; Criado, Paulo Ricardo; Peter, Jonny; Comert-Ozer, Elif; Abuzakouk, Mohamed; Agondi, Rosana Camara; Al-Ahmad, Mona; Altrichter, Sabine; Arnaout, Rand; Arruda, Luisa Karla; et al. (Allergy, 2020)
Introduction The COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown.
CRIS-Team WoS Importer:2021-01-22

The Goettingen minipig as an experimental model in wound-healing studies - Eisler, Wiebke; Held, Manuel; Rahmanian-Schwarz, Afshin; Baur, Jan-Ole; Daigeler, Adrien; Denzinger, Markus (JPRAS Open, 2024)
Background: Deep dermal wounds in extensive burns and chronic wound-healing disorders represent a significant medical problem and require a high level of therapy to reduce the risk of infection and other long-term consequences, such as amputation. A better understanding of the wound-healing processes is essential, and animal models are indispensable to fundamental research. Objective: This study aimed to provide a transparent protocol and prove the effectiveness of an in vivo porcine model using Goettingen minipigs for wound-healing studies. Material and methods: Thirteen female Goettingen minipigs were kept in species-appropriate housing and were treated according to the German law for the protection of animals. The study was performed with permission from the local ethical review committee of animal welfare. The experimental procedure for studying dermal regeneration in 102 full-thickness wounds through clinical observation and histological analysis, focusing on neodermal formation, is described in detail. Results: The Goettingen minipig model proved to be suitable in wound-healing studies. The dermal regeneration was evident and viewable without wound contamination or any rejection reaction. The histological evaluations were also reliable and clearly presented the optimized wound healing of deep dermal wounds using the different therapeutic approaches. Conclusion: Given the great clinical need for alternative or complementary therapies, we considered the Goettingen minipig trial a reliable, ethically justifiable, effective, and reproducible in vivo model for wound-healing studies.
CRIS-Team Scopus Importer:2024-05-24
Keywords: Animal model; Goettingen minipig; Tissue engineering; Wound healing

The IKZF1–IRF4/IRF5 axis controls polarization of myeloma-associated macrophages - Mougiakakos, Dimitrios; Bach, Christian; Böttcher, Martin; Beier, Fabian; Röhner, Linda; Stoll, Andrej; Rehli, Michael; Gebhard, Claudia; Lischer, Christopher; Eberhardt, Martin; Vera, Julio; Büttner-Herold, Maike; et al. (Cancer Immunology Research, 2021)
The bone marrow niche has a pivotal role in progression, survival, and drug resistance of multiple myeloma cells. Therefore, it is important to develop means for targeting the multiple myeloma bone marrow microenvironment. Myeloma-associated macrophages (MAM) in the bone marrow niche are M2 like. They provide nurturing signals to multiple myeloma cells and promote immune escape. Reprogramming M2-like macrophages toward a tumoricidal M1 phenotype represents an intriguing therapeutic strategy. This is especially interesting in view of the successful use of mAbs against multiple myeloma cells, as these therapies hold the potential to trigger macrophage-mediated phagocytosis and cytotoxicity. In this study, we observed that MAMs derived from patients treated with the immunomodulatory drug (IMiD) lenalidomide skewed phenotypically and functionally toward an M1 phenotype. Lenalidomide is known to exert its beneficial effects by modulating the CRBN-CRL4 E3 ligase to ubiquitinate and degrade the transcription factor IKAROS family zinc finger 1 (IKZF1). In M2-like MAMs, we observed enhanced IKZF1 levels that vanished through treatment with lenalidomide, yielding MAMs with a bioenergetic profile, T-cell stimulatory properties, and loss of tumor-promoting capabilities that resemble M1 cells. We also provide evidence that IMiDs interfere epigenetically, via degradation of IKZF1, with IFN regulatory factors 4 and 5, which in turn alters the balance of M1/M2 polarization. We validated our observations in vivo using the CrbnI391V mouse model that recapitulates the IMiD-triggered IKZF1 degradation. These data show a role for IKZF1 in macrophage polarization and can provide explanations for the clinical benefits observed when combining IMiDs with therapeutic antibodies. See related Spotlight on p. 254
CRIS-Team Scopus Importer:2021-03-19

The Impact of Dietary Intake of Furocoumarins and Furocoumarin-Rich Foods on the Risk of Cutaneous Melanoma: A Systematic Review - Kaiser, Isabelle; Rappl, Anja; Bolay, Lena; Pfahlberg, Annette Bettina; Heppt, Markus; Gefeller, Olaf (Nutrients, 2025)
Background/Objectives: Furocoumarins, chemical compounds found in many plant species, have a photosensitizing effect on the skin when applied topically and, by interacting with ultraviolet radiation (UVR), stimulate melanoma cells to proliferate. Whether dietary intake of furocoumarins acts as a melanoma risk factor has been investigated in several epidemiological studies, which are synthesized in our systematic review. Methods: The study protocol was registered with PROSPERO (registration number: CRD42023428596). We conducted an in-depth literature search in three databases coupled with forward and backward citation tracking and expert consultations to identify all epidemiological studies, irrespective of their design, addressing the association between a furocoumarin-containing diet and melanoma risk. We extracted information on the study details and results in a standardized manner and evaluated the risk of bias of the results using the Joanna Briggs Institute’s critical appraisal tools. Results: We identified 20 publications based on 19 different studies providing information on the association between dietary furocoumarin intake and melanoma risk. We refrained from a meta-analytical synthesis of the results because of the large heterogeneity in exposure assessment, operationalization of furocoumarin intake in the analyses, and analytical methods of the studies. In a qualitative synthesis, we found moderate evidence supporting the notion that dietary furocoumarin intake at higher levels acts as a risk factor for cutaneous melanoma. Conclusions: Our systematic review provides an overview of the current epidemiological evidence, but it could not clearly answer whether and to what extent dietary furocoumarin intake increases melanoma risk. Future epidemiological analyses focusing on this topic require more comprehensive dietary and UVR exposure data to better characterize the individual total furocoumarin intake and its interplay with UVR exposure patterns.
CRIS-Team Scopus Importer:2025-05-02
Keywords: citrus fruits; cutaneous melanoma; diet; furocoumarin; grapefruits; ultraviolet radiation

The Influence of Indisulam on Human Immune Effector Cells: Is a Combination with Immunotherapy Feasible? - Arnet, Lisa; Emilius, Lisabeth; Hamann, Annett; Carmo-Fonseca, Maria; Berking, Carola; Dörrie, Jan; Schaft, Niels (Pharmaceutics, 2025)
Background: As a modulator of pre-mRNA splicing, the anti-cancer agent indisulam can induce aberrantly spliced neoantigens, enabling immunologic anti-tumor activity. Consequently, combining indisulam with immunotherapy is expected to be a promising novel approach in cancer therapy. However, a prerequisite for such a combination is that immune effector cells remain functional and unharmed by the chemical. Methods: To ensure the immunocompetence of human immune effector cells is maintained, we investigated the influence of indisulam on ex vivo-isolated T cells and monocyte-derived dendritic cells (moDCs) from healthy donors. We used indisulam concentrations from 0.625 µM to 160 µM and examined the impact on the following: (i) the activation of CD4+ and CD8+ T cells by CD3-crosslinking and via a high-affinity TCR, (ii) the cytotoxicity of CD8+ T cells, (iii) the maturation process of moDCs, and (iv) antigen-specific CD8+ T cell priming. Results: We observed dose-dependent inhibitory effects of indisulam, and substantial inhibition occurred at concentrations around 10 µM, but the various functions of the immune system exhibited different sensitivities. The weaker activation of T cells via CD3-crosslinking was more sensitive than the stronger activation via the high-affinity TCR. T cells remained capable of killing tumor cells after treatment with indisulam up to 40 µM, but T cell cytotoxicity was impaired at 160 µM indisulam. While moDC maturation was also rather resistant, T cell priming was almost completely abolished at a concentration of 10 µM. Conclusions: These effects should be considered in possible future combinations of immunotherapy with the mRNA splicing inhibitor indisulam.
CRIS-Team Scopus Importer:2025-04-04
Keywords: dendritic cells; immunotherapy; indisulam (E7070); neoantigens; T cells

The Influence of MHC Class II on B Cell Defects Induced by Invariant Chain/CD74 N-Terminal Fragments - Schneppenheim, Janna; Loock, Ann-Christine; Huettl, Susann; Schweizer, Michaela; Luellmann-Rauch, Renate; Oberg, Hans-Heinrich; Arnold, Philipp; Lehmann, Christian; Dudziak, Diana; Kabelitz, Dieter; Lucius, Ralph; Lennon-Dumenil, Ana-Maria; et al. (Journal of Immunology, 2017)
The invariant chain (CD74) mediates assembly and targeting of MHC class II (MHCII) complexes. In endosomes, CD74 undergoes sequential degradation by different proteases, including cathepsin S (CatS) and the intramembrane protease signal peptide peptidase-like 2a (SPPL2a). In their absence, CD74 N-terminal fragments (NTFs) accumulate. In SPPL2a-/- B cells, such an NTF impairs endosomal trafficking and BCR signal transduction. In mice, this leads to a loss of splenic B cells beyond the transitional stage 1. To gain insight into CD74 determinants and the role of MHCII, we compared B cells from CatS-/- , SPPL2a-/- , and SPPL2a-MHCII double-deficient mice. We assessed differentiation of B cells in bone marrow and spleen and analyzed their endosomal morphology, BCR expression, and signal transduction. We demonstrate that MHCII is dispensable for the B cell phenotype of SPPL2a-/- mice, further supporting a CD74-intrinsic effect. Despite significant vacuolization of endosomal compartments similar to SPPL2a-/- B cells, CatS-/- traditional stage 1 B cells show unimpaired degradation of endocytic cargo, have intact BCR signaling, and do not exhibit any relevant defects in maturation. This could indicate that CD74 NTF-induced structural changes of endosomes are not directly involved in these processes. We further found that the block of CD74 degradation in CatS-/- B cells is incomplete, so that NTF levels are significantly lower than in SPPL2a-/- B cells. This suggests a dose dependency and threshold for the CD74 NTF-associated impairment of B cell signaling and maturation. In addition, different functional properties of the longer, MHCII-bound CD74 NTF could contribute to the milder phenotype of CatS-/- B cells.
EVALuna2:34373

The involvement of Toll-like receptor 9 in the pathogenesis of erosive autoimmune arthritis - Fischer, Anita; Abdollahi-Roodsaz, Shahla; Boehm, Christina; Niederreiter, Birgit; Meyer, Brigitte; Yau, Anthony C. Y.; Lonnblom, Erik; Joosten, Leo A. B.; Koenders, Marije; Lehmann, Christian; Dudziak, Diana; Krönke, Gerhard; et al. (Journal of Cellular and Molecular Medicine, 2018)
Endogenous nucleic acids and their receptors may be involved in the initiation of systemic autoimmune diseases including rheumatoid arthritis (RA). As the role of the DNA sensing Toll-like receptor (TLR) 9 in RA is unclear, we aimed to investigate its involvement in the pathogenesis of autoimmune arthritis using three different experimental models of RA. The data obtained revealed involvement of TLR9 in the T cell-dependent phase of inflammatory arthritis. In rats with pristane-induced arthritis (PIA), TLR9 inhibition before disease onset reduced arthritis significantly and almost completely abolished bone erosion. Accordingly, serum levels of IL-6, α-1-acid-glycoprotein and rheumatoid factor were reduced. Moreover, in TLR9-/- mice, streptococcal cell wall (SCW)-induced arthritis was reduced in the T cell-dependent phase, whereas T cell-independent serum-transfer arthritis was not affected. Remarkably, while TLR7 expression did not change during in vitro osteoclastogenesis, TLR9 expression was higher in precursor cells than in mature osteoclasts and partial inhibition of osteoclastogenesis was achieved only by the TLR9 antagonist. These results demonstrate a pivotal role for TLR9 in the T cell-dependent phases of inflammatory arthritis and additionally suggest some role during osteoclastogenesis. Hence, endogenous DNA seems to be crucially involved in the pathophysiology of inflammatory autoimmune arthritis.
EVALuna2:34780

The Major Immediate-Early Protein IE2 of Human Cytomegalovirus Is Sufficient to Induce Proteasomal Degradation of CD83 on Mature Dendritic Cells - Heilingloh, Christiane; Grosche, Linda; Kummer, Mirko; Mühl-Zürbes, Petra; Kamm, Lisa; Scherer, Myriam; Latzko, Melanie; Stamminger, Thomas; Steinkasserer, Alexander (Frontiers in Microbiology, 2017)
Human cytomegalovirus (HCMV) is the prototypic beta-herpesvirus and widespread throughout the human population. While infection is asymptomatic in healthy individuals, it can lead to high morbidity and mortality in immunocompromised persons. Importantly, HCMV evolved multiple strategies to interfere with immune cell function in order to establish latency in infected individuals. As mature DCs (mDCs) are antigen-presenting cells able to activate naïve T cells they play a crucial role during induction of effective antiviral immune responses. Interestingly, earlier studies demonstrated that the functionally important mDC surface molecule CD83 is down-regulated upon HCMV infection resulting in a reduced T cell stimulatory capacity of the infected cells. However, the viral effector protein and the precise mechanism of HCMV-mediated CD83 reduction remain to be discovered. Using flow cytometric analyses, we observed significant down-modulation of CD83 surface expression becoming significant already 12 h after HCMV infection. Moreover, Western bot analyses revealed that, in sharp contrast to previous studies, loss of CD83 is not restricted to the membrane-bound molecule, but also occurs intracellularly. Furthermore, inhibition of the proteasome almost completely restored CD83 surface expression during HCMV infection. Results of infection kinetics and cycloheximide-actinomycin D-chase experiments, strongly suggested that an HCMV immediate early gene product is responsible for the induction of CD83 down-modulation. Consequently, we were able to identify the major immediate early protein IE2 as the viral effector protein that induces proteasomal CD83 degradation.
EVALuna2:26039

The Nectin-1 Expression correlates with the Susceptibility of malignant Melanoma to oncolytic Herpes Simplex Viruses in vitro and in vivo - Schwertner, B.; Linder, G.; Stauner, C. Toledo; Klapproth, E.; Magnus, C.; Rohrhofer, A.; Gross, S.; Schuler-Thurner, Beatrice; Oettl, V.; Feichtgruber, N.; Drexler, K.; Evert, K.; et al. (JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, 2021)
CRIS-Team WoS Importer:2021-09-24

The need for regular training in skin cancer screening: a cross-sectional study among general practitioners in Germany - Steeb, Theresa; Reinhardt, Lydia; Strasser, C.; Wessely, Anja; Schelling, J.; Petzold, Anne; Heppt, Markus; Meier, Friedegund; Berking, Carola (Journal of the European Academy of Dermatology and Venereology, 2022)
CRIS-Team Scopus Importer:2022-07-15

The Neural Crest Transcription Factor SOX10 is essential for the Survival of Uveal Melanoma Cells - Wessely, A.; Kammerbauer, C.; Berking, Carola; Heppt, Markus (JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, 2020)
CRIS-Team WoS Importer:2020-09-11

The novel role of lymphatic vessels in the pathogenesis of ocular diseases - Clahsen, Thomas; Hadrian, Karina; Notara, Maria; Schlereth, Simona L.; Howaldt, Antonia; Prokosch, Verena; Volatier, Thomas; Hos, Deniz; Schroedl, Falk; Kaser-Eichberger, Alexandra; Heindl, Ludwig M.; Steven, Philipp; et al. (Progress in Retinal and Eye Research, 2023)
Historically, the eye has been considered as an organ free of lymphatic vessels. In recent years, however, it became evident, that lymphatic vessels or lymphatic-like vessels contribute to several ocular pathologies at various peri- and intraocular locations. The aim of this review is to outline the pathogenetic role of ocular lymphatics, the respective molecular mechanisms and to discuss current and future therapeutic options based thereon. We will give an overview on the vascular anatomy of the healthy ocular surface and the molecular mechanisms contributing to corneal (lymph)angiogenic privilege. In addition, we present (i) current insights into the cellular and molecular mechanisms occurring during pathological neovascularization of the cornea triggered e.g. by inflammation or trauma, (ii) the role of lymphatic vessels in different ocular surface pathologies such as dry eye disease, corneal graft rejection, ocular graft versus host disease, allergy, and pterygium, (iii) the involvement of lymphatic vessels in ocular tumors and metastasis, and (iv) the novel role of the lymphatic-like structure of Schlemm's canal in glaucoma. Identification of the underlying molecular mechanisms and of novel modulators of lymphangiogenesis will contribute to the development of new therapeutic targets for the treatment of ocular diseases associated with pathological lymphangiogenesis in the future. The preclinical data presented here outline novel therapeutic concepts for promoting transplant survival, inhibiting metastasis of ocular tumors, reducing inflammation of the ocular surface, and treating glaucoma. Initial data from clinical trials suggest first success of novel treatment strategies to promote transplant survival based on pretransplant corneal lymphangioregression.
CRIS-Team Scopus Importer:2023-06-30
Keywords: Corneal (lymph)angiogenic privilege; Corneal immune reaction; Glaucoma; Limbal stem cells; Lymphangiogenesis; Transplantation

The ontogenetic path of human dendritic cells - Amon, Lukas; Lehmann, Christian; Heger, Lukas; Heidkamp, Gordon Frederik; Dudziak, Diana (Molecular Immunology, 2020)
Dendritic cells (DCs) orchestrate adaptive immune responses. In healthy individuals, DCs are drivers and fine-tuners of T cell responses directed against invading pathogens or cancer cells. In parallel, DCs control autoreactive T cells, thereby maintaining T cell tolerance. Under various disease conditions, a disruption of this delicate balance can lead to chronic infections, tumor evasion, or autoimmunity. While great efforts have been made to unravel the origin and development of this powerful cell type in mice, only little is known about the ontogeny of human DCs. Here, we summarize the current understanding of the developmental path of DCs from hematopoietic stem cells to fully functional DCs in their local tissue environment and provide a template for the identification of DCs across various tissues.
CRIS-Team Scopus Importer:2020-03-06
Keywords: Conventional; DC; Human; Ontogeny; Progeny; Transcription factor

The outweigh of toxicity versus risk of recurrence for adjuvant interferon therapy: a survey in German melanoma patients and their treating physicians - Kähler, Katharina C.; Blome, Christine; Forschner, Andrea; Gutzmer, Ralf; Hauschild, Axel; Heinzerling, Lucie; Livingstone, Elisabeth; Loquai, Carmen; Müller-Brenne, Tina; Schadendorf, Dirk; Utikal, Jochen; Wagner, Tobias; et al. (Oncotarget, 2018)
After more than two decades with interferon alfa-2a and 2b (IFN) as the only approved drugs in the adjuvant setting for melanoma, new treatment approaches like immune checkpoint inhibitors and BRAF-MEK inhibitors improve the progression free survival (PFS) and also the overall survival (OS). We compared physicians' preferences ("utilities") for health states associated with IFN therapy to their patients' preferences. Utilities describe a preference for a specific health state on a scale of 0 (as bad as death) to 1.0 (perfect health). Setting: We assessed utilities for health states associated with adjuvant IFN using the standard gamble technique in 108 physicians and 130 melanoma patients. Four IFN toxicity scenarios and three outcome scenarios were given to the participants. Both groups were asked for the 5-year disease free survival (DFS) they would need to accept the described IFN-related side effects. Results: In both groups, utilities for melanoma relapse were significantly lower than for IFN side effects, showing that toxicity was more acceptable than relapse. Physicians indicated higher utilities for each scenario and needed lower 5-year DFS both in case of mild-to-moderate and severe side effects. Patients were willing to tolerate mild-to-moderate and severe toxicity for a 50% and 75% chance of 5-year DFS, while physicians only required a chance of 40% and 50%, respectively. Conclusion: Both physicians and patients rated melanoma recurrence much lower than even severe IFN side effects. In direct comparison, physicians rated cancer-related scenarios more positively and accepted IFN toxicity for an even lower treatment benefit.
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The p.Arg435His Variation of IgG3 With High Affinity to FcRn Is Associated With Susceptibility for Pemphigus Vulgaris-Analysis of Four Different Ethnic Cohorts - Recke, Andreas; Konitzer, Sarah; Lemcke, Susanne; Freitag, Miriam; Sommer, Nele Maxi; Abdelhady, Mohammad; Amoli, Mahsa M.; Benoit, Sandrine; El-Chennawy, Farha; Eldarouti, Mohammad; Eming, Ruediger; Glaeser, Regine; et al. (Frontiers in Immunology, 2018)
IgG3 is the IgG subclass with the strongest effector functions among all four IgG subclasses and the highest degree of allelic variability among all constant immunoglobulin genes. Due to its genetic position, IgG3 is often the first isotype an antibody switches to before IgG1 or IgG4. Compared with the other IgG subclasses, it has a reduced half-life which is probably connected to a decreased affinity to the neonatal Fc receptor (FcRn). However, a few allelic variants harbor an amino acid replacement of His435 to Arg that reverts the half-life of the resulting IgG3 to the same level as the other IgG subclasses. Because of its functional impact, we hypothesized that the p.Arg435His variation could be associated with susceptibility to autoantibody-mediated diseases like pemphigus vulgaris (PV) and bullous pemphigoid (BP). Using a set of samples from German, Turkish, Egyptian, and Iranian patients and controls, we were able to demonstrate a genetic association of the p.Arg435His variation with PV risk, but not with BP risk. Our results suggest a hitherto unknown role for the function of IgG3 in the pathogenesis of PV.
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The Quality of Guidelines for the Treatment of Cutaneous Melanoma: A methodological Assessment - Steeb, Theresa; Wessely, A.; Drexler, K.; Salzmann, M.; Toussaint, Frédéric; Heinzerling, Lucie; Reinholz, M.; Berking, Carola; Heppt, Markus (JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, 2020)
CRIS-Team WoS Importer:2020-09-11

The quality of national skin cancer screening from the perspective of general practitioners: A questionnaire-based comparison between Saxony and Bavaria (SaBaScreen) - Strasser, C.; Reinhardt, L.; Steeb, Theresa; Wessely, Anja; Schelling, Jörg; Petzold, Anne; Heppt, Markus; Meier, F.; Berking, Carola (JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, 2022)
CRIS-Team WoS Importer:2022-09-23

The quality of practice guidelines for melanoma: A methodologic appraisal with the agree ii and agree-rex instruments - Steeb, Theresa; Wessely, Anja; Drexler, Konstantin; Salzmann, Martin; Toussaint, Frédéric; Heinzerling, Lucie; Reinholz, Markus; Berking, Carola; Heppt, Markus (Cancers, 2020)
Multiple guidelines on cutaneous melanoma (CM) are available from several consortia and countries. To provide up-to-date guidance in the rapidly changing field of melanoma treatment, guideline developers have to provide regular updates without compromises of quality. We performed a systematic search in guideline databases, Medline and Embase to identify guidelines on CM. The methodological quality of the identified guidelines was independently assessed by five reviewers using the instruments “Appraisal of Guidelines for Research and Evaluation” (AGREE II) and “Recommendation EXcellence” (AGREE-REX). We performed descriptive analysis, explored subgroup differences using the Kruskal–Wallis (H) test and examined the relationship between distinct domains and items of the instruments with Spearman’s correlation. Six guidelines by consortia from Australia, France, Germany, Scotland, Spain and the United States of America were included. The German guideline fulfilled 71%–98% of criteria in AGREE II and 78%–96% for AGREE-REX, obtaining the highest scores. Deficiencies in the domains of “applicability” and “values and preferences” were observed in all guidelines. The German and Spanish guidelines significantly differed from each other in most of the domains. The domains “applicability” and “values and preferences” were identified as methodological weaknesses requiring careful revision and improvement in the future.
CRIS-Team Scopus Importer:2020-06-26
Keywords: AGREE; Cutaneous melanoma; Level of evidence; Melanoma treatment; Practice guideline

Therapeutic cancer vaccination with ex vivo rna-transfected dendritic cells—an update - Dörrie, Jan; Schaft, Niels; Schuler, Gerold; Schuler-Thurner, Beatrice (Pharmaceutics, 2020)
Over the last two decades, dendritic cell (DC) vaccination has been studied extensively as active immunotherapy in cancer treatment and has been proven safe in all clinical trials both with respect to short and long-term side effects. For antigen-loading of dendritic cells (DCs) one method is to introduce mRNA coding for the desired antigens. To target the whole antigenic repertoire of a tumor, even the total tumor mRNA of a macrodissected biopsy sample can be used. To date, reports have been published on a total of 781 patients suffering from different tumor entities and HIV-infection, who have been treated with DCs loaded with mRNA. The majority of those were melanoma patients, followed by HIV-infected patients, but leukemias, brain tumors, prostate cancer, renal cell carcinomas, pancreatic cancers and several others have also been treated. Next to antigen-loading, mRNA-electroporation allows a purposeful manipulation of the DCs’ phenotype and function to enhance their immunogenicity. In this review, we intend to give a comprehensive summary of what has been published regarding clinical testing of ex vivo generated mRNA-transfected DCs, with respect to safety and risk/benefit evaluations, choice of tumor antigens and RNA-source, and the design of better DCs for vaccination by transfection of mRNA-encoded functional proteins.
CRIS-Team Scopus Importer:2020-02-04
Keywords: Clinical trial; Dendritic cells; Electroporation; Immunotherapy; RNA; Therapeutic vaccination

Therapeutische Optionen der Necrobiosis lipoidica - Erfurt-Berge, Cornelia; Arnet, Lisa (Internistische Praxis, 2023)
Necrobiosis lipoidica (NL) is a granulomatous inflammatory skin disease with characteristic yellow-brown, central atrophic plaques, which usually occur pretibially on both lower legs. The diagnosis is often made based on the typical clinical presentation. In case of equivocal findings, a biopsy can rule out differential diagnoses. Because it is a rare disease and the pathogenesis is still poorly understood, there are currently no guidelines for the targeted, standard treatment of NL patients. Typically, NL usually develops in middle age and affects women more frequently. In addition, NL is often observed in combination with endocrine disorders such as diabetes mellitus or thyroid dysfunction. Also discussed is an association with metabolic syndrome, which may additionally favor the development of ulcerations and thus complicate the course of the disease. Various topical and systemic therapeutic options are available, occasionally in combination. The use of topical corticosteroids is recommended by experts generally. Some patients may benefit from topical calcineurin inhibitors, compression therapy, or phototherapy. In case of recalcitrant or ulcerated lesions, systemic therapy is often initiated. In this regard, systemic corticosteroids are used as the primary option. However, off-label therapies such as fumaric acid esters, dapsone, biologics, or JAK inhibitors have also shown promising effects in some case reports. However, due to the lack of randomized trials with large patient collectives, the efficacy of individual therapeutic options cannot be conclusively evaluated.
CRIS-Team Scopus Importer:2023-10-20
Keywords: chronic wounds; granulomatous dermatosis; necrobiosis lipoidica; systemic therapy

Therapeutische Optionen der Necrobiosis lipoidica - Erfurt-Berge, Cornelia; Arnet, Lisa (Tägliche Praxis, 2023)
Necrobiosis lipoidica (NL) is a granulomatous inflammatory skin disease with characteristic yellow-brown, central atrophic plaques, which usually occur pretibially on both lower legs. The diagnosis is often made based on the typical clinical presentation. In case of equivocal findings, a biopsy can rule out differential diagnoses. Because it is a rare disease and the pathogenesis is still poorly understood, there are currently no guidelines for the targeted, standard treatment of NL patients. Typically, NL usually develops in middle age and affects women more frequently. In addition, NL is often observed in combination with endocrine disorders such as diabetes mellitus or thyroid dysfunction. Also discussed is an association with metabolic syndrome, which may additionally favor the development of ulcerations and thus complicate the course of the disease. Various topical and systemic therapeutic options are available, occasionally in combination. The use of topical corticosteroids is recommended by experts generally. Some patients may benefit from topical calcineurin inhibitors, compression therapy, or phototherapy. In case of recalcitrant or ulcerated lesions, systemic therapy is often initiated. In this regard, systemic corticosteroids are used as the primary option. However, offlabel therapies such as fumaric acid esters, dapsone, biologics, or JAK inhibitors have also shown promising effects in some case reports. However, due to the lack of randomized trials with large patient collectives, the efficacy of individual therapeutic options cannot be conclusively evaluated.
CRIS-Team Scopus Importer:2024-12-16
Keywords: chronic wounds; granulomatous dermatosis; necrobiosis lipoidica; systemic therapy

Therapy Management of the first Recurrence after adjuvant Therapy in Stage III: multicenter real-world Data - Lodde, G.; Forschner, A.; Hassel, J. C.; Wulfken, L. M.; Meier, F.; Mohr, P.; Kaehler, K.; Schilling, B.; Loquai, C.; Berking, Carola; Huening, S.; Eckardt, J.; et al. (JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, 2022)
CRIS-Team WoS Importer:2022-09-23

Therapy Options for Patients with Advanced Basal Cell Carcinoma - Kirchberger, M. C. (JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, 2019)
CRIS-Team WoS Importer:2019-05-17

Therapy preferences in melanoma treatment - willingness to pay and preference of quality versus length of life of patients, physicians and healthy controls - Krammer, Ramona; Heinzerling, Lucie (PLoS ONE, 2014)
New melanoma therapies, like e.g. ipilimumab, improve survival. However, only a small subset of patients benefits while 60% encounter side effects. Furthermore, these marginal benefits come at a very high price of EUR110'000 per treatment. This study examines attitudes towards melanoma therapy options of physicians, healthy individuals and patients, their willingness to pay and preference of quality versus length of life.Based on findings from a focus group questionnaires were developed and pretested. After obtaining ethical approval and informed consent surveys were conducted in a total of 90 participants (n = 30 for each group). Statistical analyses were conducted using R.Attitudes vastly differed between healthy participants, physicians and melanoma patients. Whereas melanoma patients show a high willingness to endure side effects despite very small survival gains (down to 1 extra week) or even only hope with no survival benefit, healthy controls are more critical, while physicians are the most therapy adverse. Consequently, if given EUR100'000 and the free decision what to spend the money on the willingness to pay for therapy was much higher in the patient group (68%) compared to 28% of healthy controls and only 43% of the physicians, respectively. When lowering the amount of cash that could be received instead of ipilimumab to EUR50'000 or EUR10'000 to test price sensitivity 69% (+1%) and 76% (+8%) of melanoma patients, respectively, preferred ipilimumab over cash. When judging on societal spending even melanoma patients opted for spending on ipilimumab in only 21%.The judgment about the benefits of new treatment options largely differs between groups, physicians being the most critical against therapy. Price elasticity was low.
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Therapy preferences in melanoma treatment—Willingness to pay and preference of quality versus length of life of patients, physicians, healthy individuals and physicians with oncological disease - Weiß, Julia; Kirchberger, Michael; Heinzerling, Lucie (Cancer Medicine, 2020)
Background: In recent years, monoclonal antibodies such as ipilimumab, nivolumab, and pembrolizumab have made a significant impact on the treatment of advanced melanoma. Combination of immune checkpoint inhibitors leads to improved survival and response rates of 58%-61% as compared to monotherapy (36%-44%). However, the price for the better response rates is also a higher frequency of severe adverse events (59%) as compared to monotherapy (17%-21%). This study examines attitudes towards melanoma therapy options of physicians, healthy individuals, melanoma patients, and physicians with oncological disease, their willingness to pay, and preference of quality versus length of life. Methods: After obtaining ethical approval and informed consent surveys were conducted in 111 participants divided into four groups: melanoma patients (n = 30), healthy individuals as controls (n = 30), physicians (n = 27), and physicians with oncological disease (n = 24). Statistical analyses were conducted using SPSS statistics (version 25, IBM), applying the Pearson´s chi-squared test, Spearman correlation coefficient, Wilcoxon-Mann-Whitney test, and Kruskal-Wallis test. Results: Life prolongation is more valued by melanoma patients and physicians with oncological disease compared to healthy controls and healthy physicians. In total, 30% of melanoma patients opt for a life prolonging therapy in all cases, even if this life prolongation is only marginal. Physicians are the strongest proponents of combination immunotherapy. Conclusion: The valuation of the different treatment options differs in the four study groups with affected people valuing life prolongation much more. The individual value of cancer therapies is high, but differs from the societal standpoint.
CRIS-Team Scopus Importer:2020-07-24
Keywords: cancer management; clinical guidelines; immunology; quality of life

The RNA world in the 21st century-a systems approach to finding non-coding keys to clinical questions - Schmitz, Ulf; Naderi-Meshkin, Hojjat; Gupta, Shailendra K.; Wolkenhauer, Olaf; Vera, Julio (Briefings in Bioinformatics, 2016)
There was evidence that RNAs are a functionally rich class of molecules not only since the arrival of the next-generation sequencing technology. Non-coding RNAs (ncRNA) could be the key to accelerated diagnosis and enhanced prediction of disease and therapy outcomes as well as the design of advanced therapeutic strategies to overcome yet unsatisfactory approaches.In this review, we discuss the state of the art in RNA systems biology with focus on the application in the systems biomedicine field. We propose guidelines for analysing the role of microRNAs and long non-coding RNAs in human pathologies. We introduce RNA expression profiling and network approaches for the identification of stable and effective RNomics-based biomarkers, providing insights into the role of ncRNAs in disease regulation. Towards this, we discuss ways to model the dynamics of gene regulatory networks and signalling pathways that involve ncRNAs. We also describe data resources and computational methods for finding putative mechanisms of action of ncRNAs. Finally, we discuss avenues for the computer-aided design of novel RNA-based therapeutics.
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The Road to Effective Cancer Immunotherapy—A Computational Perspective on Tumor Epitopes in Anti-Cancer Immunotherapy - Lischer, Christopher; Vera González, Julio (Systems Medicine, 2021)
A current option for anti-cancer immunotherapy is to make use of epitopes which can guide cytotoxic T cells to destroy the tumor. It is however difficult to find immunogenic epitopes which engage the T cells sufficiently to fight cancer effectively. Additionally, cancer heterogeneity makes the development of such epitopes even more difficult since there is little general overlap between two cancers. Hence an epitope-based approach requires the use of many modern aspects of biological science like bioinformatics, next-generation sequencing and biostatistics. In this article, we provide a broad introduction to the topic from a computational perspective and offer insights into current paradigms of data-driven epitope selection, explain some fundamental workflows and outline avenues for future research in vitro and in silico.<br
Keywords: Antigen presentation; Bioinformatics; Cancer; Decision support systems; Epitopes; Immunoinformatics; Immunology; Immunotherapy; Introduction; Systems biology; Workflows

The role of age, neutrophil infiltration and antibiotics timing in the severity of streptococcus pneumoniae pneumonia. Insights from a multi-level mathematical model approach - Santos, Guido; Vera, Julio (International Journal of Molecular Sciences, 2020)
Bacterial pneumonia is one of the most prevalent infectious diseases and has high mortality in sensitive patients (children, elderly and immunocompromised). Although an infection, the disease alters the alveolar epithelium homeostasis and hinders normal breathing, often with fatal consequences. A special case is hospitalized aged patients, which present a high risk of infection and death because of the community acquired version of the Streptococcus pneumoniae pneumonia. There is evidence that early antibiotics treatment decreases the inflammatory response during pneumonia. Here, we investigate mechanistically this strategy using a multi-level mathematical model, which describes the 24 first hours after infection of a single alveolus from the key signaling networks behind activation of the epithelium to the dynamics of the local immune response. With the model, we simulated pneumonia in aged and young patients subjected to different antibiotics timing. The results show that providing antibiotics to elderly patients 8 h in advance compared to young patients restores in aged individuals the effective response seen in young ones. This result suggests the use of early, probably prophylactic, antibiotics treatment in aged hospitalized people with high risk of pneumonia.
CRIS-Team Scopus Importer:2020-11-20
Keywords: Inflammation; Macrophages; Mathematical model; Monocytes; Multi-level; Neutrophils; Pneumonia; Streptococcus pneumoniae

The role of cooperativity in a p53-miR34 dynamical mathematical model - Nikolov, Svetoslav; Wolkenhauer, Olaf; Vera, Julio; Nenov, Momchil (Journal of Theoretical Biology, 2020)
The objective of this study is to evaluate the role of cooperativity, captured by the Hill coefficient, in a minimal mathematical model describing the interactions between p53 and miR-34a. The model equations are analyzed for negative, none and normal cooperativity using a specific version of bifurcation theory and they are solved numerically. Special attention is paid to the sign of so-called first Lyapunov value. Interpretations of the results are given, both according to dynamic theory and in biological terms. In terms of cell signaling, we propose the hypothesis that when the outgoing signal of a system spends a physiologically significant amount of time outside of its equilibrium state, then the value of that signal can be sampled at any point along the trajectory towards that equilibrium and indeed, at multiple points. Coupled with non-linear behavior, such as that caused by cooperativity, this feature can account for a complex and varied response, which p53 is known for. From dynamical point of view, we found that when cooperativity is negative, the system has only one stable equilibrium point. In the absence of cooperativity, there is a single unstable equilibrium point with a critical boundary of stability. In the case with normal cooperativity, the system can have one, two, or three steady states with both, bi-stability and bi-instability occurring.
CRIS-Team Scopus Importer:2020-04-14
Keywords: Cooperativity; Numerical analysis; p53-miR34 dynamics; Qualitative analysis

The role of immune checkpoint blockade in uveal melanoma - Wessely, Anja; Steeb, Theresa; Erdmann, Michael; Heinzerling, Lucie; Vera, Julio; Schlaak, Max; Berking, Carola; Heppt, Markus (International Journal of Molecular Sciences, 2020)
Uveal melanoma (UM) represents the most common intraocular malignancy in adults and accounts for about 5% of all melanomas. Primary disease can be effectively controlled by several local therapy options, but UM has a high potential for metastatic spread, especially to the liver. Despite its clinical and genetic heterogeneity, therapy of metastatic UM has largely been adopted from cutaneous melanoma (CM) with discouraging results until now. The introduction of antibodies targeting CTLA-4 and PD-1 for immune checkpoint blockade (ICB) has revolutionized the field of cancer therapy and has achieved pioneering results in metastatic CM. Thus, expectations were high that patients with metastatic UM would also benefit from these new therapy options. This review provides a comprehensive and up-to-date overview on the role of ICB in UM. We give a summary of UM biology, its clinical features, and how it differs from CM. The results of several studies that have been investigating ICB in metastatic UM are presented. We discuss possible reasons for the lack of efficacy of ICB in UM compared to CM, highlight the pitfalls of ICB in this cancer entity, and explain why other immune-modulating therapies could still be an option for future UM therapies.
CRIS-Team Scopus Importer:2020-02-14
Keywords: CTLA-4; Cytotoxic T lymphocyte-associated antigen; Immune checkpoint blockade; Ipilimumab; Nivolumab; Ocular melanoma; PD-1; Pembrolizumab; Programmed death 1; Uveal melanoma

The Role of MicroRNAs in Cancer Biology and Therapy from a Systems Biology Perspective - Lai, Xin; Schmitz, Ulf; Vera, Julio (Springer, 2022)
Since the discovery of microRNAs (miRNAs) in Caenorhabditis elegans, our understanding of their cellular function has progressed continuously. Today, we have a good understanding of miRNA-mediated gene regulation, miRNA-mediated cross talk between genes including competing endogenous RNAs, and miRNA-mediated signaling transduction both in normal human physiology and in diseases. Besides, these noncoding RNAs have shown their value for clinical applications, especially in an oncological context. They can be used as reliable biomarkers for cancer diagnosis and prognosis and attract increasing attention as potential therapeutic targets. Many achievements made in the miRNA field are based on joint efforts from computational and molecular biologists. Systems biology approaches, which integrate computational and experimental methods, have played a fundamental role in uncovering the cellular functions of miRNAs. In this chapter, we review and discuss the role of miRNAs in oncology from a system biology perspective. We first describe biological facts about miRNA genetics and function. Next, we discuss the role of miRNAs in cancer progression and review the application of miRNAs in cancer diagnostics and therapy. Finally, we elaborate on the role that miRNAs play in cancer gene regulatory networks. Taken together, we emphasize the importance of systems biology approaches in our continued efforts to study miRNA cancer regulation.
CRIS-Team Scopus Importer:2022-12-02
Keywords: Bioinformatics; Circulating miRNA; Mathematical modelling; Metastamir; mRNA destabilization; Network biology; Oncomir; Posttranscriptional gene regulation; Translation repression; Tumor suppressor miRNA

The Role of Non-coding RNAs in Tumorigenesis, Diagnosis/Prognosis, and Therapeutic Strategies for Cutaneous Melanoma - Schaft, Niels; Dörrie, Jan (Methods in Molecular Biology, 2025)
RNA is a substance with various biological functions. It serves as blueprint for proteins and shuttles information from the genes to the protein factories of the cells. However, these factories-the ribosomes-are also composed mainly of RNA, whose purpose is not storing information but enzymatic action. In addition, there is a cornucopia of RNA molecules within our cells that form a complex regulatory network, connected with all aspects of cellular development and maintenance. These non-coding RNAs can be used for diagnostics and therapeutic strategies in cancer. In this chapter we give an overview of recent developments in non-coding RNA-based diagnostics and therapies for cutaneous melanoma. It is not meant to be comprehensive; however, it describes examples based on some of the most recent publications in this field.
CRIS-Team Scopus Importer:2025-01-31
Keywords: circular RNA; Immune checkpoint resistance; Kinase inhibitor resistance; Long non-coding RNA; microRNA; RNA-based therapy

The Role of the Large T Antigen in the Molecular Pathogenesis of Merkel Cell Carcinoma - Myrda, Julia; Bremm, Franziska; Schaft, Niels; Dörrie, Jan (Genes, 2024)
The large T antigen (LT) of the Merkel cell polyomavirus (MCPyV) is crucial for Merkel cell carcinoma (MCC), a rare but very aggressive form of neuroendocrine skin cancer. The clonal integration of MCPyV DNA into the host genome is a signature event of this malignancy. The resulting expression of oncogenes, including the small T (sT) antigen and a truncated form of the LT (truncLT), directly contribute to carcinogenesis. The truncation of the C-terminus of LT prevents the virus from replicating due to the loss of the origin binding domain (OBD) and the helicase domain. This precludes cytopathic effects that would lead to DNA damage and ultimately cell death. At the same time, the LxCxE motif in the N-terminus is retained, allowing truncLT to bind the retinoblastoma protein (pRb), a cellular tumor suppressor. The continuously inactivated pRb promotes cell proliferation and tumor development. truncLT exerts several classical functions of an oncogene: altering the host cell cycle, suppressing innate immune responses to viral DNA, causing immune escape, and shifting metabolism in favor of cancer cells. Given its central role in MCC, the LT is a major target for therapeutic interventions with novel approaches, such as immune checkpoint inhibition, T cell-based immunotherapy, and cancer vaccines.
CRIS-Team Scopus Importer:2024-10-04
Keywords: antigen-based immunotherapy; cell cycle regulation; immune escape; Merkel cell carcinoma; Merkel cell polyomavirus; viral carcinogenesis

The side effect registry immuno-oncology (SERIO) – A tool for systematic analysis of immunotherapy-induced side effects - Ertl, Carolin; Ruf, Theresa; Mentzer, Dirk; Kong, Mingzi; Kramer, Rafaela; Bergwelt-Baildon, Michael von; Subklewe, Marion; Tomsitz, Dirk; Ascierto, Paolo A.; Dummer, Reinhard; Gogas, Helen; Lebbé, Celeste; et al. (European Journal of Cancer, 2024)
Background: Immunotherapies such as immune checkpoint inhibitors (ICI) are effective in multiple tumor entities but induce a plethora of side effects. Comprehensive real-world analyses are essential to identify new signals, characterize diagnostic features, enable risk assessment, determine pathomechanisms, assess effectiveness of side effect management and compare tumor outcomes. Methods: The international online `Side-Effect Registry Immuno-Oncology´ (SERIO; www.serio-registry.org) collects rare, complex, and severe immunotherapy-induced side effects across all tumor entities with a strong focus on ICI-induced immune-related adverse events (irAE). The relational database management system (RDMS) contains structured data on patient and tumor characteristics, type of immunotherapy, treatment of side effects, and outcome of tumor and irAE. Data are captured within 25 organ modules including new modules for immune effector cell-associated neurotoxicity syndrome (ICANS) for CAR-T-cell therapies and cytokine release syndrome (CRS) for bispecific antibodies. Information on biological samples is gathered. Results: A total of 1398 irAE cases have been documented by 58 centers from 13 countries in patients with 17 tumor types. IrAEs were induced by nine different immunotherapies including tebentafusp and CAR-T cell therapies, and resulted, among others, in neurological (7.6%), pulmonary (4.0%), and cardiac toxicities (2.9%). 50.0% of all irAEs were graded severe or life-threatening and 23.0% of patients received second-line therapy for steroid-refractory or steroid-dependent irAE. SERIO has contributed to 44 original publications on topics ranging from irMyocarditis to irEncephalitis to long-term persistent sequelae of immunotherapy. Conclusions: A reliable evidence base is crucial for decision-making in rare, complex or therapy-refractory irAE. SERIO can help optimize side effect management and thereby reduce morbidity and mortality induced by immunotherapy.
CRIS-Team Scopus Importer:2024-02-16
Keywords: Bispecific antibodies; CAR-T-cells; Checkpoint inhibitors; Data base; Immune-related adverse events; Online registry

The simultaneous siRNA-mediated downregulation of inhibitory receptors to improve CAR-T cell immunotherapy of melanoma - Simon, B.; Harrer, D.; Weide, B.; Schuler, Gerold; Schuler-Thurner, Beatrice; Dörrie, Jan; Schaft, Niels; Uslu, Ugur (2017)
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