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

Abstract

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.

Keywords: CD8+ T cell; ID2; IL-12; antitumor therapy efficacy; butyrate; gut microbial metabolites.