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Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota.

作者信息

Vétizou Marie, Pitt Jonathan M, Daillère Romain, Lepage Patricia, Waldschmitt Nadine, Flament Caroline, Rusakiewicz Sylvie, Routy Bertrand, Roberti Maria P, Duong Connie P M, Poirier-Colame Vichnou, Roux Antoine, Becharef Sonia, Formenti Silvia, Golden Encouse, Cording Sascha, Eberl Gerard, Schlitzer Andreas, Ginhoux Florent, Mani Sridhar, Yamazaki Takahiro, Jacquelot Nicolas, Enot David P, Bérard Marion, Nigou Jérôme, Opolon Paule, Eggermont Alexander, Woerther Paul-Louis, Chachaty Elisabeth, Chaput Nathalie, Robert Caroline, Mateus Christina, Kroemer Guido, Raoult Didier, Boneca Ivo Gomperts, Carbonnel Franck, Chamaillard Mathias, Zitvogel Laurence

机构信息

Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, Villejuif, France. University of Paris Sud XI, Kremlin-Bicêtre, France.

Institut National de la Recherche Agronomique (INRA), Micalis-UMR1319, 78360 Jouy-en-Josas, France.

出版信息

Science. 2015 Nov 27;350(6264):1079-84. doi: 10.1126/science.aad1329. Epub 2015 Nov 5.

DOI:10.1126/science.aad1329
PMID:26541610
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4721659/
Abstract

Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, T cell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis-specific T cells. Fecal microbial transplantation from humans to mice confirmed that treatment of melanoma patients with antibodies against CTLA-4 favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade.

摘要

相似文献

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[5]
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[9]
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[10]
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本文引用的文献

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