Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8+ T cell immunity
| Autor: | Wenyan Wang, Yiping Li, Xiaohuan Guo, Charles R. Mackay, Jiaoyan Huang, Xin Dong, Yun Chen, Yang Xin Fu, Yao He, Quanbo Wang, Liuhui Fu, Jing Zhang, Mingli Gong |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Tumor microenvironment biology Physiology Chemistry Cell Biology Butyrate Gut flora biology.organism_classification 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Immunity Cancer research Interleukin 12 Cytotoxic T cell Signal transduction Molecular Biology 030217 neurology & neurosurgery CD8 |
| Zdroj: | Cell Metabolism. 33:988-1000.e7 |
| ISSN: | 1550-4131 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|