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Bauer, V. ; Ahmetlic, F. ; Hömberg, N. ; Geishauser, A. ; Röcken, M.* ; Mocikat, R.

Immune checkpoint blockade impairs immunosuppressive mechanisms of regulatory T cells in B-cell lymphoma.

Transl. Oncol. 14:101170 (2021)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
In malignant disease, CD4+Foxp3+ regulatory T cells (Tregs) hamper antitumor immune responses and may provide a target for immunotherapy. Although immune checkpoint blockade (ICB) has become an established therapy for several cancer entities including lymphoma, its mechanisms have not been entirely uncovered. Using endogenously arising λ-MYC-transgenic mouse B-cell lymphomas, which can effectively be suppressed by either Treg ablation or ICB, we investigated which mechanisms are used by Tregs to suppress antitumor responses and how ICB affects these pathways. During tumor development, Tregs up-regulated Foxp3, CD25, CTLA-4 and IL-10, which correlated with enhanced immunosuppressive functions. Thus, in contrast to other tumors, Tregs did not become dysfunctional despite chronic stimulation in the tumor microenvironment and progressive up-regulation of PD-1. Immunosuppression was mediated by direct contacts between Tregs and effector T cells and by IL-10. When λ-MYC mice were treated with ICB antibodies, Tregs revealed a less profound up-regulation of Foxp3, CD25 and IL-10 and a decreased suppressive capacity. This may be due to the shift towards a pro-inflammatory milieu fostered by ICB. In summary, an ICB-induced interference with Treg-dependent immunosuppression may contribute to the success of ICB.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Ctla-4 ; Foxp3 ; Il-10 ; Myc Lymphoma ; Pd-1; Transcription Factor Foxp3; Costimulatory Molecules; Pd-1 Blockade; Cancer; Self; Instability; Activation; Expression; Generation; Receptors
e-ISSN 1936-5233
Journal Translational Oncology
Quellenangaben Volume: 14, Issue: 9, Pages: , Article Number: 101170 Supplement: ,
Publisher Neoplasia Press
Publishing Place Ste 800, 230 Park Ave, New York, Ny 10169 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) AG Translationale Molekulare Immunologie (TMI)
Grants Deutsche Forschungsgemeinschaft
WilhelmSanderStiftung
Deutsche Krebshilfe