Decitabine priming increases anti-PD-1 antitumor efficacy by promoting CD8+ progenitor exhausted T cell expansion in tumor models.

ABSTRACT: CD8+ exhausted T cells (Tex) are heterogeneous. PD-1 inhibitors reinvigorate progenitor Tex, which subsequently differentiate into irresponsive terminal Tex. The ability to maintain a capacity for durable proliferation of progenitor Tex is important, but the mechanism remains unclear. Here, we showed CD8+ progenitor Tex pretreated with decitabine, a low-dose DNA demethylating agent, had enhanced proliferation and effector function against tumors after anti-PD-1 treatment in vitro. Treatment with decitabine plus anti-PD-1 promoted the activation and expansion of tumor-infiltrated CD8+ progenitor Tex and efficiently suppressed tumor growth in multiple tumor models. Transcriptional and epigenetic profiling of tumor-infiltrated T cells demonstrated that the combination of decitabine plus anti-

SUBMITTER: Li X 

PROVIDER: S-EPMC10065084 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature