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Pelzl, R.* ; Benintende, G.* ; Gsottberger, F.* ; Scholz, J.K.* ; Ruebner, 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.* ; Huebner, H.* ; Schett, G.* ; Mackensen, A.* ; Laurenti, L.* ; Graw, F.* ; Völkl, S.* ; Nganou-Makamdop, K.* ; Müller, F.*

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

Blood 146, 1300-1313 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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 breast cancer and AML survivors. Identified alterations persisted beyond five years of ongoing complete remission and in DLBCL correlated with increased pro-inflammatory markers such as IL-6, B2M, or sCD14. The chronic inflammation was associated with functionally blunted T-cell immunity against SARS-CoV-2-specific peptides and reduced responses correlated with reduced Tn-cells. Persisting inflammation was confirmed by deep sequencing and by cytokine profiles, together pointing towards 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Chronic Inflammation; T-cells; Microbiome; Cancer; Expansion; Survivors; Disease
Sprache englisch
Veröffentlichungsjahr 2025
HGF-Berichtsjahr 2025
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Zeitschrift Blood
Quellenangaben Band: 146, Heft: 11, Seiten: 1300-1313 Artikelnummer: , Supplement: ,
Verlag American Society of Hematology
Verlagsort Radarweg 29, 1043 Nx Amsterdam, Netherlands
Begutachtungsstatus Peer reviewed
Institut(e) CF Metabolomics & Proteomics (CF-MPC)
POF Topic(s) 30203 - Molecular Targets and Therapies
PSP-Element(e) A-630700-001
Förderungen NOTICE clinician scientist program of the Deutsche Forschungsgemeinschaft
Hightech Agenda Bavaria
Deutsche Forschungsgemeinschaft
Deutsche Jose Carreras Leukamie-Stiftung
Gilead
Bundesministerium fur Bildung und Forschung
Bayerisches Zentrum fur Krebsforschung
Deutsche Krebshilfe (DKH)
DOI 10.1182/blood.2024027877
WOS ID 001573586100011
Scopus ID 105008086880
PubMed ID 40359478
Erfassungsdatum 2025-05-15
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