Lenalidomide enhances MOR202-dependent macrophage-mediated effector functions via the vitamin D pathway

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Busch L, Mougiakakos D, Büttner-Herold M, Müller MJ, Volmer DA, Bach C, Fabri M, Bittenbring JT, Neumann F, Boxhammer R, Nolting J, Bisht S, Böttcher M, Jitschin S, Hoffmann M, Balzer H, Beier F, Gezer D, Dudziak D, Gelse K, Hennig F, Pallasch CP, Spriewald B, Mackensen A, Bruns H
Zeitschrift: Leukemia
Jahr der Veröffentlichung: 2018
ISSN: 0887-6924


Abstract

Macrophages are key mediators of the therapeutic effects exerted by monoclonal antibodies, such as the anti-CD38 antibody MOR202, currently introduced in multiple myeloma (MM) therapy. Therefore, it is important to understand how antibody-mediated effector functions of myeloma-associated macrophages (MAMs) are regulated. Here, we focused on the effects of vitamin D, a known regulator of macrophage effector functions. Consequently, it was the aim of this study to assess whether modulation of the vitamin D pathway alters the tumoricidal activity of MAMs. Here, we demonstrate that MAMs display a defective vitamin D pathway with reduced expression level of CYP27B1 and limited tumoricidal activity which can be restored by the IMiD lenalidomide in vitro. Furthermore, our data indicate that the vitamin D pathway of MAMs from MM patients does recover during an IMiD-containing therapy shown by an improved MOR202-mediated cytotoxic activity of these MAMs against primary MM cells ex vivo. Here, the ex vivo cytotoxic activity could be further enhanced by vitamin D supplementation. These data suggest that vitamin D holds a key role for the effector functions of MAMs and that vitamin D supplementation in IMiD combination trials could further increase the therapeutic efficacy of anti-CD38 antibodies such as MOR202, which remains to be investigated in clinical studies.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Bach, Christian Dr. rer. nat.
Medizinische Klinik 5 - Hämatologie und Internistische Onkologie
Böttcher, Martin Dr. rer. nat.
Medizinische Klinik 5 - Hämatologie und Internistische Onkologie
Bruns, Heiko PD Dr.
Medizinische Klinik 5 - Hämatologie und Internistische Onkologie
Dudziak, Diana Prof. Dr.
Professur für die Biologie Dendritischer Zellen
Hennig, Friedrich Prof. Dr.
Unfallchirurgische Abteilung in der Chirurgischen Klinik
Medizinische Klinik 3 - Rheumatologie und Immunologie
Mackensen, Andreas Prof. Dr.
Lehrstuhl für Innere Medizin V
Mougiakakos, Dimitrios
Professur für Hämatologie/Onkologie mit dem Schwerpunkt Tumorimmunologie


Einrichtungen weiterer Autorinnen und Autoren

MorphoSys AG
Universität des Saarlandes (UdS)
Universität Köln
Universitätsklinikum Aachen
Universitätsklinikum Bonn
Universitätsklinikum des Saarlandes
Universitätsklinikum Köln


Zitierweisen

APA:
Busch, L., Mougiakakos, D., Büttner-Herold, M., Müller, M.J., Volmer, D.A., Bach, C.,... Bruns, H. (2018). Lenalidomide enhances MOR202-dependent macrophage-mediated effector functions via the vitamin D pathway. Leukemia. https://dx.doi.org/10.1038/s41375-018-0114-0

MLA:
Busch, Leonhard, et al. "Lenalidomide enhances MOR202-dependent macrophage-mediated effector functions via the vitamin D pathway." Leukemia (2018).

BibTeX: 

Zuletzt aktualisiert 2018-05-11 um 15:38