The microbial metabolite trimethylamine N-oxide promotes antitumor immunity in triple-negative breast cancer
The microbial metabolite trimethylamine N-oxide promotes antitumor immunity in triple-negative breast cancer
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DOI：
10.1016/j.cmet.2022.02.010
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发表时间：
2022-04-05
期刊：
影响因子：
29
通讯作者：
Shao, Zhi-Ming
中科院分区：
文献类型：
--
作者：
Wang, Hai;Rong, Xingyu;Shao, Zhi-Ming
Immunotherapy has achieved limited success in patients with triple-negative breast cancer (TNBC), an aggressive disease with a poor prognosis. Commensal microbiota have been proven to colonize the mammary gland, but whether and how they modulate the tumor microenvironment remains elusive. We performed a multiomics analysis of a cohort of patients with TNBC (n = 360) and found genera under Clostridiales, and the related metabolite trimethylamine N-oxide (TMAO) was more abundant in tumors with an activated immune microenvironment. Patients with higher plasma TMAO achieved better responses to immunotherapy. Mechanistically, TMAO induced pyroptosis in tumor cells by activating the endoplasmic reticulum stress kinase PERK and thus enhanced CD8(+) T cell-mediated antitumor immunity in TNBC in vivo. Collectively, our findings offer new insights into microbiota-metabolite-immune crosstalk and indicate that microbial metabolites, such as TMAO or its precursor choline, may represent a novel therapeutic strategy to promote the efficacy of immunotherapy in TNBC.
