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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

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 m...

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Autores principales: Sun, Shan, Luo, Lingjie, Liang, Wenhua, Yin, Qian, Guo, Jing, Rush, Anthony M., Lv, Zhibao, Liang, Qiming, Fischbach, Michael A., Sonnenburg, Justin L., Dodd, Dylan, Davis, Mark M., Wang, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959554/
https://www.ncbi.nlm.nih.gov/pubmed/33077598
http://dx.doi.org/10.1073/pnas.1921223117
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author Sun, Shan
Luo, Lingjie
Liang, Wenhua
Yin, Qian
Guo, Jing
Rush, Anthony M.
Lv, Zhibao
Liang, Qiming
Fischbach, Michael A.
Sonnenburg, Justin L.
Dodd, Dylan
Davis, Mark M.
Wang, Feng
author_facet Sun, Shan
Luo, Lingjie
Liang, Wenhua
Yin, Qian
Guo, Jing
Rush, Anthony M.
Lv, Zhibao
Liang, Qiming
Fischbach, Michael A.
Sonnenburg, Justin L.
Dodd, Dylan
Davis, Mark M.
Wang, Feng
author_sort Sun, Shan
collection PubMed
description 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.
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spelling pubmed-79595542021-03-22 Bifidobacterium alters the gut microbiota and modulates the functional metabolism of T regulatory cells in the context of immune checkpoint blockade Sun, Shan Luo, Lingjie Liang, Wenhua Yin, Qian Guo, Jing Rush, Anthony M. Lv, Zhibao Liang, Qiming Fischbach, Michael A. Sonnenburg, Justin L. Dodd, Dylan Davis, Mark M. Wang, Feng Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2020-11-03 2020-10-19 /pmc/articles/PMC7959554/ /pubmed/33077598 http://dx.doi.org/10.1073/pnas.1921223117 Text en Copyright © 2020 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Sun, Shan
Luo, Lingjie
Liang, Wenhua
Yin, Qian
Guo, Jing
Rush, Anthony M.
Lv, Zhibao
Liang, Qiming
Fischbach, Michael A.
Sonnenburg, Justin L.
Dodd, Dylan
Davis, Mark M.
Wang, Feng
Bifidobacterium alters the gut microbiota and modulates the functional metabolism of T regulatory cells in the context of immune checkpoint blockade
title Bifidobacterium alters the gut microbiota and modulates the functional metabolism of T regulatory cells in the context of immune checkpoint blockade
title_full Bifidobacterium alters the gut microbiota and modulates the functional metabolism of T regulatory cells in the context of immune checkpoint blockade
title_fullStr Bifidobacterium alters the gut microbiota and modulates the functional metabolism of T regulatory cells in the context of immune checkpoint blockade
title_full_unstemmed Bifidobacterium alters the gut microbiota and modulates the functional metabolism of T regulatory cells in the context of immune checkpoint blockade
title_short Bifidobacterium alters the gut microbiota and modulates the functional metabolism of T regulatory cells in the context of immune checkpoint blockade
title_sort bifidobacterium alters the gut microbiota and modulates the functional metabolism of t regulatory cells in the context of immune checkpoint blockade
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959554/
https://www.ncbi.nlm.nih.gov/pubmed/33077598
http://dx.doi.org/10.1073/pnas.1921223117
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