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

Yao He, Liuhui Fu, Yiping Li, Wenyan Wang, Mingli Gong, Jing Zhang, Xin Dong, Jiaoyan Huang, Quanbo Wang, Charles R. Mackay, Yang Xin Fu, Yun Chen, Xiaohuan Guo

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)988-1000.e7
JournalCell Metabolism
Volume33
Issue number5
DOIs
StatePublished - May 4 2021

Keywords

  • CD8+ T cell
  • ID2
  • IL-12
  • antitumor therapy efficacy
  • butyrate
  • gut microbial metabolites

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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