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

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. [Display omitted] •Gut microbial metabolites improve chemotherapy efficacy via regulating CD8+ T cells•The SCFA butyrate directly boosts the antitumor CD8+ T cell response via ID2•ID2 regulates the function of CD8+ T cells through IL-12 signaling•Butyrate supplementation improves the antitumor therapy efficacy He et al. report that the gut microbial metabolite butyrate can directly modulate antitumor CD8+ T cell response and improve the chemotherapy efficacy through ID2-dependent IL-12 signaling, suggesting that manipulation of gut microbial metabolites could be effective as a part of cancer therapy.