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

نویسندگان

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

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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عنوان ژورنال:
  • Science

دوره 350 6264  شماره 

صفحات  -

تاریخ انتشار 2015