Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8+ T cell immunity.

By Yao He, Liuhui Fu, Yiping Li, Wenyan Wang, M. Gong, Jing Zhang, Xin Dong, Jiaoyan Huang, Quanbo Wang, C. Mackay and 3 more. Cell Metabolism, 2021

630 citations recorded by the source corpus.

Recent studies in both mice and humans have suggested that gut microbiota could modulate tumor responsiveness to chemo- or immunotherapies. However, the underlying mechanism is not clear yet. Here, we found that gut microbial metabolites, especially butyrate, could promote the efficacy of oxaliplatin by modulating CD8+ T cell function in the tumor microenvironment. Butyrate treatment directly boosted the antitumor cytotoxic CD8+ T cell responses both in vitro and in vivo in an ID2-dependent manner by promoting the IL-12 signaling pathway. In humans, the oxaliplatin responder cancer patients exhibited a higher amount of serum butyrate than did non-responders, which could also increase ID2 expression and function of human CD8+ T cells. Together, our findings suggest that the gut microbial metabolite butyrate could promote antitumor therapeutic efficacy through the ID2-dependent regulation of CD8+ T cell immunity, indicating that gut microbial metabolites could be effective as a part of cancer therapy.

Subfields: Biological Psychiatry, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/97104ae8d413904bba3fae9d4a97eeb402daa1a9