细胞毒性T细胞
丁酸盐
肠道菌群
CD8型
免疫
免疫系统
生物
肿瘤微环境
癌症研究
T细胞
免疫学
药理学
体外
生物化学
发酵
作者
Yu He,Liuhui Fu,Yiping Li,Wenyan Wang,Mingli Gong,Jing Zhang,Xin Dong,Jiaoyan Huang,Quanbo Wang,Charles Mackay,Yang Xin Fu,Yun Chen,Xiaohuan Guo
出处
期刊:Cell Metabolism
[Elsevier]
日期:2021-05-01
卷期号:33 (5): 988-1000.e7
被引量:284
标识
DOI:10.1016/j.cmet.2021.03.002
摘要
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.
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