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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 P. Roberti, Connie P.M. Duong, Vichnou Poirier-Colame, Antoine Roux, Sonia Becharef, Silvia C. Formenti, Encouse B. Golden

Science · 2015 · ▲ 3,392 citations

Dysbiosis Human Mouse

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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.

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Provenance

Source: OpenAlex
DOI: 10.1126/science.aad1329
Canonical: link ↗
Fetched: 2026-06-12 MST

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APA

Vétizou, M., Pitt, J.M., Daillère, R., Lepage, P., Waldschmitt, N., Flament, C., Rusakiewicz, S., Routy, B., Roberti, M.P., Duong, C.P., Poirier-Colame, V., Roux, A., Becharef, S., Formenti, S.C., Golden, E.B., Cording, S., Eberl, G., Schlitzer, A., Ginhoux, F., & Mani, S. (2015). Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. <em>Science</em>. https://doi.org/10.1126/science.aad1329

Vancouver

Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N, Flament C, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015. doi:10.1126/science.aad1329.

BibTeX

@unpublished{marie2015Antica, title = {Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota}, author = {Marie Vétizou and Jonathan M. Pitt and Romain Daillère and Patricia Lepage and Nadine Waldschmitt and Caroline Flament and Sylvie Rusakiewicz and Bertrand Routy and María P. Roberti and Connie P.M. Duong and Vichnou Poirier-Colame and Antoine Roux and Sonia Becharef and Silvia C. Formenti and Encouse B. Golden and Sascha Cording and Gérard Eberl and Andreas Schlitzer and Florent Ginhoux and Sridhar Mani and Takahiro Yamazaki and Nicolas Jacquelot and David Enot and M Bérard and Jérôme Nigou}, journal = {Science}, year = {2015}, doi = {10.1126/science.aad1329}, }