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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)
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Il-10 ; Lymphoma ; Th1 Cells ; Tr1 Cells ; Tumor Escape ; C-myc
ISSN (print) / ISBN
0304-3835
e-ISSN
0304-3835
Journal
Cancer Letters
Quellenangaben
Volume: 503,
Pages: 110-116
Publisher
Elsevier
Publishing Place
Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
AG Translationale Molekulare Immunologie (TMI)
CF Immunoanalytics (IMA)
CF Immunoanalytics (IMA)
Grants
Deutsche Forschungsgemeinschaft (Cluster of Excellence iFIT)
Deutsche Forschungsgemeinschaft
Wilhelm-Sander-Stiftung
Deutsche Krebshilfe
Deutsche Forschungsgemeinschaft
Wilhelm-Sander-Stiftung
Deutsche Krebshilfe