The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide

Sophie Viaud; Fabiana Saccheri; Grégoire Mignot; Takahiro Yamazaki; Romain Daillère; Dalil Hannani; David P. Enot; Christina Pfirschke; Camilla Engblom; Mikael J. Pittet; Andreas Schlitzer; Florent Ginhoux; Lionel Apetoh; Elisabeth Chachaty; Paul Louis Woerther; Gérard Eberl; Marion Bérard; Chantal Ecobichon; Dominique Clermont; Chantal Bizet; Valérie Gaboriau-Routhiau; Nadine Cerf-Bensussan; Paule Opolon; Nadia Yessaad; Eric Vivier; Bernhard Ryffel; Charles O. Elson; Joël Doré; Guido Kroemer; Patricia Lepage; Ivo Gomperts Boneca; François Ghiringhelli; Laurence Zitvogel

doi:10.1126/science.1240537

The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide

Sophie Viaud, Fabiana Saccheri, Grégoire Mignot, Takahiro Yamazaki, Romain Daillère, Dalil Hannani, David P. Enot, Christina Pfirschke, Camilla Engblom, Mikael J. Pittet, Andreas Schlitzer, Florent Ginhoux, Lionel Apetoh, Elisabeth Chachaty, Paul Louis Woerther, Gérard Eberl, Marion Bérard, Chantal Ecobichon, Dominique Clermont, Chantal BizetValérie Gaboriau-Routhiau, Nadine Cerf-Bensussan, Paule Opolon, Nadia Yessaad, Eric Vivier, Bernhard Ryffel, Charles O. Elson, Joël Doré, Guido Kroemer, Patricia Lepage, Ivo Gomperts Boneca, François Ghiringhelli, Laurence Zitvogel

Istituto Europeo di Oncologia

Research output: Contribution to journal › Article › peer-review

Abstract

Cyclophosphamide is one of several clinically important cancer drugs whose therapeutic efficacy is due in part to their ability to stimulate antitumor immune responses. Studying mouse models, we demonstrate that cyclophosphamide alters the composition of microbiota in the small intestine and induces the translocation of selected species of Gram-positive bacteria into secondary lymphoid organs. There, these bacteria stimulate the generation of a specific subset of "pathogenic" T helper 17 (pT_H17) cells and memory T_H1 immune responses. Tumor-bearing mice that were germ-free or that had been treated with antibiotics to kill Gram-positive bacteria showed a reduction in pT_H17 responses, and their tumors were resistant to cyclophosphamide. Adoptive transfer of pT_H17 cells partially restored the antitumor efficacy of cyclophosphamide. These results suggest that the gut microbiota help shape the anticancer immune response.

Original language	English
Pages (from-to)	971-976
Number of pages	6
Journal	Science
Volume	342
Issue number	6161
DOIs	https://doi.org/10.1126/science.1240537
Publication status	Published - 2013

ASJC Scopus subject areas

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History and Philosophy of Science
Medicine(all)

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Viaud, S., Saccheri, F., Mignot, G., Yamazaki, T., Daillère, R., Hannani, D., Enot, D. P., Pfirschke, C., Engblom, C., Pittet, M. J., Schlitzer, A., Ginhoux, F., Apetoh, L., Chachaty, E., Woerther, P. L., Eberl, G., Bérard, M., Ecobichon, C., Clermont, D., ... Zitvogel, L. (2013). The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science, 342(6161), 971-976. https://doi.org/10.1126/science.1240537

Viaud, S, Saccheri, F, Mignot, G, Yamazaki, T, Daillère, R, Hannani, D, Enot, DP, Pfirschke, C, Engblom, C, Pittet, MJ, Schlitzer, A, Ginhoux, F, Apetoh, L, Chachaty, E, Woerther, PL, Eberl, G, Bérard, M, Ecobichon, C, Clermont, D, Bizet, C, Gaboriau-Routhiau, V, Cerf-Bensussan, N, Opolon, P, Yessaad, N, Vivier, E, Ryffel, B, Elson, CO, Doré, J, Kroemer, G, Lepage, P, Boneca, IG, Ghiringhelli, F & Zitvogel, L 2013, 'The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide', Science, vol. 342, no. 6161, pp. 971-976. https://doi.org/10.1126/science.1240537

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abstract = "Cyclophosphamide is one of several clinically important cancer drugs whose therapeutic efficacy is due in part to their ability to stimulate antitumor immune responses. Studying mouse models, we demonstrate that cyclophosphamide alters the composition of microbiota in the small intestine and induces the translocation of selected species of Gram-positive bacteria into secondary lymphoid organs. There, these bacteria stimulate the generation of a specific subset of {"}pathogenic{"} T helper 17 (pTH17) cells and memory TH1 immune responses. Tumor-bearing mice that were germ-free or that had been treated with antibiotics to kill Gram-positive bacteria showed a reduction in pTH17 responses, and their tumors were resistant to cyclophosphamide. Adoptive transfer of pTH17 cells partially restored the antitumor efficacy of cyclophosphamide. These results suggest that the gut microbiota help shape the anticancer immune response.",

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AU - Viaud, Sophie

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AU - Hannani, Dalil

AU - Enot, David P.

AU - Pfirschke, Christina

AU - Engblom, Camilla

AU - Pittet, Mikael J.

AU - Schlitzer, Andreas

AU - Ginhoux, Florent

AU - Apetoh, Lionel

AU - Chachaty, Elisabeth

AU - Woerther, Paul Louis

AU - Eberl, Gérard

AU - Bérard, Marion

AU - Ecobichon, Chantal

AU - Clermont, Dominique

AU - Bizet, Chantal

AU - Gaboriau-Routhiau, Valérie

AU - Cerf-Bensussan, Nadine

AU - Opolon, Paule

AU - Yessaad, Nadia

AU - Vivier, Eric

AU - Ryffel, Bernhard

AU - Elson, Charles O.

AU - Doré, Joël

AU - Kroemer, Guido

AU - Lepage, Patricia

AU - Boneca, Ivo Gomperts

AU - Ghiringhelli, François

AU - Zitvogel, Laurence

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The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide

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