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

Marie Vétizou 1, 2 Jonathan M. Pitt 1, 2 Romain Daillere 1, 2 Patricia Lepage 3 Nadine Waldschmitt 4 Caroline Flament 2, 5 Sylvie Rusakiewicz 2, 5 Bertrand Routy 1, 2, 5 Maria P. Roberti 2, 5 Connie P. M. Duong 2, 5 Vichnou Poirier-Colame 2, 5 Antoine Roux 6, 2 Sonia Becharef 2, 5 Silvia Formenti 7 Encouse Golden 7 Sascha Cording 8 Gerard Eberl 8 Andreas Schlitzer 9 Florent Ginhoux 9 Sridhar Mani 10 Takahiro Yamazaki 2, 5 Nicolas Jacquelot 1, 2 David P. Enot 6, 10 Marion Bérard 11 Jérôme Nigou 12 Paule Opolon 13 Alexander Eggermont 13, 2 Paul-Louis Woerther 13 Elisabeth Chachaty 13 Nathalie Chaput 14 Caroline Robert 14 Christina Mateus 13 Guido Kroemer 15, 16, 17 Didier Raoult 18 Ivo Gomperts Boneca 19 Franck Carbonnel 20 Mathias Chamaillard 4 Laurence Zitvogel 1, 2, 5, *
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, Tcell 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.
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Submitted on : Wednesday, March 17, 2021 - 9:35:50 AM
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Marie Vétizou, Jonathan M. Pitt, Romain Daillere, Patricia Lepage, Nadine Waldschmitt, et al.. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science, American Association for the Advancement of Science, 2015, 350 (6264), pp.1079-1084. ⟨10.1126/science.aad1329⟩. ⟨hal-02639698⟩

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