Large B-cell lymphoma imprints a dysfunctional immune phenotype that persists years after treatment

Pelzl R, Benintende G, Gsottberger F, Scholz JK, Rübner M, Yao H, Wendland K, Rejeski K, Altmann H, Petkovic S, Mellenthin L, Kübel S, Schmiedeberg M, Klein P, Petrera A, Baur R, Eckstein S, Hoepffner-Grundy S, Röllig C, Subklewe M, Hübner H, Schett G, Mackensen A, Laurenti L, Graw F, Völkl S, Nganou-Makamdop K, Müller F (2025)

Publication Language: English

Publication Type: Journal article

Publication year: 2025

Journal

Blood American Society of Hematology

Book Volume: 146

Pages Range: 1300-1313

Journal Issue: 11

DOI: 10.1182/blood.2024027877

Abstract

Immunotherapy has become standard of care in the treatment of diffuse large B-cell lymphoma (DLBCL). Changes in immunophenotypes observed at first diagnosis predict therapy outcome but little is known about the resolution of these alterations in remission. Comprehensive characterization of immune changes from fresh, peripheral whole blood revealed a functionally relevant increase of myeloid-derived suppressor cells, reduced naïve T cells, and an increase of activated and terminally differentiated T cells before treatment, which aggravated after therapy. Suggesting causal relation, injection of lymphoma in mice induced similar changes in the murine T cells. Distinct immune imprints were found in those who have survived breast cancer and acute myeloid leukemia. Identified alterations persisted beyond 5 years of ongoing complete remission and correlated with increased proinflammatory markers such as interleukin-6, β2-microglobulin, or soluble CD14 in DLBCL. The chronic inflammation was associated with functionally blunted T-cell immunity against severe acute respiratory syndrome coronavirus 2–specific peptides, and reduced responses correlated with reduced naïve T cells. Persisting inflammation was confirmed by deep sequencing and by cytokine profiles, together pointing toward a compensatory activation of innate immunity. The persisting, lymphoma-induced immune alterations in remission may explain long-term complications, have implications for vaccine strategies, and are likely relevant for immunotherapies.

Authors with CRIS profile

Richard Pelzl Professur für CAR-T-Zell-Therapie Giulia Benintende Department of Medicine 5 – Haematology and Oncology Franziska Gsottberger Department of Medicine 5 – Haematology and Oncology Julia Scholz Department of Medicine 5 – Haematology and Oncology Matthias Rübner Department of Obstetrics and Gynaecology Kerstin Wendland Department of Medicine 5 – Haematology and Oncology Sabrina Kübel Lehrstuhl für Klinische und Molekulare Virologie Moritz Schmiedeberg Institute of Clinical and Molecular Virology Paulina Klein Institute of Clinical and Molecular Virology Rebecca Baur Department of Medicine 5 – Haematology and Oncology Sophie Eckstein Department of Obstetrics and Gynaecology Hanna Hübner Department of Obstetrics and Gynaecology Georg Schett Lehrstuhl für Innere Medizin III Andreas Mackensen Lehrstuhl für Innere Medizin V Frederik Graw Professur für Modellierung von Immunprozessen Simon Völkl Department of Medicine 5 – Haematology and Oncology Christiane Krystelle Nganou Makamdop Institute of Clinical and Molecular Virology Fabian Müller Department of Medicine 5 – Haematology and Oncology

Involved external institutions

Bayerisches Zentrum für Krebsforschung (BZKF) DE Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) Catholic University of the Sacred Heart / Università Cattolica del Sacro Cuore IT Italy (IT)

How to cite

APA:

Pelzl, R., Benintende, G., Gsottberger, F., Scholz, J.K., Rübner, M., Yao, H.,... Müller, F. (2025). Large B-cell lymphoma imprints a dysfunctional immune phenotype that persists years after treatment. Blood, 146(11), 1300-1313. https://doi.org/10.1182/blood.2024027877

MLA:

Pelzl, Richard, et al. "Large B-cell lymphoma imprints a dysfunctional immune phenotype that persists years after treatment." Blood 146.11 (2025): 1300-1313.

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