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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)
Verlagsversion Forschungsdaten 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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
Zeitschrift Translational Oncology
Quellenangaben Band: 14, Heft: 9, Seiten: , Artikelnummer: 101170 Supplement: ,
Verlag Neoplasia Press
Verlagsort Ste 800, 230 Park Ave, New York, Ny 10169 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) AG Translationale Molekulare Immunologie (TMI)
Förderungen Deutsche Forschungsgemeinschaft
WilhelmSanderStiftung
Deutsche Krebshilfe