期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 218, 期 3, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20201915
关键词
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资金
- Ludwig Cancer Research Foundation
- National Institutes of Health/National Cancer Institute [R21 CA227528, R21 CA231273-01]
The gut microbiota influences tumor control following ionizing radiation by altering the abundance of butyrate-producing bacteria, which can enhance tumor sensitivity to radiation.
The antitumor effects of ionizing radiation (IR) are mediated in part through activation of innate and adaptive immunity. Here we report that gut microbiota influences tumor control following IR. Vancomycin decreased the abundance of butyrate producing gut bacteria and enhanced antitumor responses to IR. Oral administration of Lachnospiraceae, a family of vancomycin-sensitive bacteria, was associated with increased systemic and intratumoral butyric acid levels and impaired the efficacy of IR in germ-free (GF) mice. Local butyrate inhibited STING-activated type I IFN expression in dendritic cells (DCs) through blockade of TBK1 and IRF3 phosphorylation, which abrogated IR-induced tumor-specific cytotoxic T cell immune responses without directly protecting tumor cells from radiation. Our findings demonstrate that the selective targeting of butyrate-producing microbiota may provide a novel therapeutic option to enhance tumor radiation sensitivity.
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