Interruption of the intratumor CD8⁺ T cell:Treg crosstalk improves the efficacy of PD-1 immunotherapy.

ABSTRACT: PD-1 blockade unleashes potent antitumor activity in CD8⁺ T cells but can also promote immunosuppressive T regulatory (Treg) cells, which may worsen the response to immunotherapy. Tumor-Treg inhibition is a promising strategy to improve the efficacy of checkpoint blockade immunotherapy; however, our understanding of the mechanisms supporting tumor-Tregs during PD-1 immunotherapy is incomplete. Here, we show that PD-1 blockade increases tumor-Tregs in mouse models of melanoma and metastatic melanoma patients. Mechanistically, Treg accumulation is not caused by Treg-intrinsic inhibition of PD-1 signaling but depends on an indirect effect of activated CD8⁺ T cells. CD8⁺ T cells produce IL-2 and colocalize with Tregs in mouse and human melanomas. IL-2 upregulat

SUBMITTER: Geels SN 

PROVIDER: S-EPMC11285091 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature