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Ma, Y. ; Bauer, V. ; Riedel, T. ; Ahmetlic, F. ; Hömberg, N. ; Hofer, T.P. ; Röcken, M.* ; Mocikat, R.

Interleukin-10 counteracts T-helper type 1 responses in B-cell lymphoma and is a target for tumor immunotherapy.

Cancer Lett. 503, 110-116 (2021)
Postprint DOI PMC
Open Access Green
To establish strategies for immunotherapy of B-cell lymphoma, it is mandatory to gain deeper insights into the mechanisms of tumor immune escape. In a mouse model of endogenously arising lymphoma, we investigated the impact of IL-10 on the regulation of antitumor responses. Despite progressive functional impairment of NK cells and lack of IFN-γ in the tumor milieu, we found an augmented fraction of T helper type 1 (Th1) cells, which continued to express IFN-γ but also upregulated IL-10 during disease development. Using a lymphoma microenvironment in vitro, we showed that Th1 cells were converted to Foxp3-negative T regulatory type 1 (Tr1) cells, which coexpressed IFN-γ and IL-10 and upregulated PD-1. This differentiation required pre-existing IL-10, which was primarily provided by malignant B cells and dendritic cells. IFN-γ only declined in cells with the uppermost PD-1 levels. Importantly, antibody-mediated IL-10 ablation in vivo improved effector cell functions and significantly suppressed tumor development. While the contribution of IL-10 to cancer immune escape has been controversially discussed in the past, we show that IL-10 suppresses ongoing, potentially protective immune responses in lymphoma and might be a target for immunotherapy.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Il-10 ; Lymphoma ; Th1 Cells ; Tr1 Cells ; Tumor Escape ; C-myc
ISSN (print) / ISBN 0304-3835
e-ISSN 0304-3835
Zeitschrift Cancer Letters
Quellenangaben Band: 503, Heft: , Seiten: 110-116 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) AG Translationale Molekulare Immunologie (TMI)
Institute of Virology (VIRO)
Förderungen Deutsche Forschungsgemeinschaft (Cluster of Excellence iFIT)
Deutsche Forschungsgemeinschaft
Wilhelm-Sander-Stiftung
Deutsche Krebshilfe