| Literature DB >> 26541610 |
Marie Vétizou1, Jonathan M Pitt1, Romain Daillère1, Patricia Lepage2, Nadine Waldschmitt3, Caroline Flament4, Sylvie Rusakiewicz4, Bertrand Routy5, Maria P Roberti4, Connie P M Duong4, Vichnou Poirier-Colame4, Antoine Roux6, Sonia Becharef4, Silvia Formenti7, Encouse Golden7, Sascha Cording8, Gerard Eberl8, Andreas Schlitzer9, Florent Ginhoux9, Sridhar Mani10, Takahiro Yamazaki4, Nicolas Jacquelot1, David P Enot11, Marion Bérard12, Jérôme Nigou13, Paule Opolon14, Alexander Eggermont15, Paul-Louis Woerther16, Elisabeth Chachaty16, Nathalie Chaput17, Caroline Robert18, Christina Mateus19, Guido Kroemer20, Didier Raoult21, Ivo Gomperts Boneca22, Franck Carbonnel23, Mathias Chamaillard3, Laurence Zitvogel24.
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.Entities:
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Year: 2015 PMID： 26541610 PMCID： PMC4721659 DOI： 10.1126/science.aad1329
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728