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 language | English (US) |
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Pages (from-to) | 988-1000.e7 |
Journal | Cell Metabolism |
Volume | 33 |
Issue number | 5 |
DOIs | |
State | Published - 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