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Bifidobacterium alters the gut microbiota and modulates the functional metabolism of T regulatory cells in the context of immune checkpoint blockade.


ABSTRACT: Immune checkpoint-blocking antibodies that attenuate immune tolerance have been used to effectively treat cancer, but they can also trigger severe immune-related adverse events. Previously, we found that Bifidobacterium could mitigate intestinal immunopathology in the context of CTLA-4 blockade in mice. Here we examined the mechanism underlying this process. We found that Bifidobacterium altered the composition of the gut microbiota systematically in a regulatory T cell (Treg)-dependent manner. Moreover, this altered commensal community enhanced both the mitochondrial fitness and the IL-10-mediated suppressive functions of intestinal Tregs, contributing to the amelioration of colitis during immune checkpoint blockade.

SUBMITTER: Sun S 

PROVIDER: S-EPMC7959554 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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<i>Bifidobacterium</i> alters the gut microbiota and modulates the functional metabolism of T regulatory cells in the context of immune checkpoint blockade.

Sun Shan S   Luo Lingjie L   Liang Wenhua W   Yin Qian Q   Guo Jing J   Rush Anthony M AM   Lv Zhibao Z   Liang Qiming Q   Fischbach Michael A MA   Sonnenburg Justin L JL   Dodd Dylan D   Davis Mark M MM   Wang Feng F  

Proceedings of the National Academy of Sciences of the United States of America 20201019 44


Immune checkpoint-blocking antibodies that attenuate immune tolerance have been used to effectively treat cancer, but they can also trigger severe immune-related adverse events. Previously, we found that <i>Bifidobacterium</i> could mitigate intestinal immunopathology in the context of CTLA-4 blockade in mice. Here we examined the mechanism underlying this process. We found that <i>Bifidobacterium</i> altered the composition of the gut microbiota systematically in a regulatory T cell (Treg)-depe  ...[more]

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