Microbial metabolite butyrate promotes anti-PD-1 antitumor efficacy by modulating T cell receptor signaling of cytotoxic CD8 T cell.

ABSTRACT: Recent studies have demonstrated that the antitumor immunity of immune cells can be modulated by gut microbiota and their metabolites. However, the underlying mechanisms remain unclear. Here, we showed that the serum butyric acid level is positively correlated with the expression of programmed cell death-1 (PD-1) on circulating CD8⁺ and Vγ9 Vδ2 (Vδ2⁺) T cells in patients with non-small cell lung cancer (NSCLC). Responder NSCLC patients exhibited higher levels of serum acetic acid, propionic acid, and butyric acid than non-responders. Depletion of the gut microbiota reduces butyrate levels in both feces and serum in tumor-bearing mice. Mechanistically, butyrate increased histone 3 lysine 27 acetylation (H3K27ac) at the promoter region of Pdcd1 and Cd28 in

SUBMITTER: Zhu X 

PROVIDER: S-EPMC10464552 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature