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

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

Bacteroides fragilis

Blockade

CTLA-4

2015

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.

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“Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota” is a paper by Marie Vétizou Jonathan M. Pitt Romain Daillère Patricia Lepage Nadine Waldschmitt Caroline Flament Sylvie Rusakiewicz Bertrand Routy María Paula Roberti Connie P.M. Duong Vichnou Poirier-Colame Antoine Roux Sonia Becharef Silvia C. Formenti Encouse B. Golden Sascha Cording Gérard Eberl Andreas Schlitzer Florent Ginhoux Sridhar Mani Takahiro Yamazaki Nicolas Jacquelot David Enot M Bérard Jérôme Nigou Paule Opolon Alexander M.M. Eggermont Paul‐Louis Woerther Élisabeth Chachaty Nathalie Chaput Caroline Robert C. Mateus Guido Kroemer Didier Raoult Ivo Gomperts Boneca Franck Carbonnel Mathias Chamaillard Laurence Zitvogel published in 2015. It has an Open Access status of “green”. You can read and download a PDF Full Text of this paper here.