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

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

1542 Citations (Scopus)

Résumé

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.

langue originale	Anglais
Pages (de - à)	971-976
Nombre de pages	6
journal	Science
Volume	342
Numéro de publication	6161
Les DOIs	https://doi.org/10.1126/science.1240537
état	Publié - 1 janv. 2013

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10.1126/science.1240537

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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

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title = "The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide",

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.",

author = "Sophie Viaud and Fabiana Saccheri and Gr{\'e}goire Mignot and Takahiro Yamazaki and Romain Daill{\`e}re and Dalil Hannani and Enot, {David P.} and Christina Pfirschke and Camilla Engblom and Pittet, {Mikael J.} and Andreas Schlitzer and Florent Ginhoux and Lionel Apetoh and Elisabeth Chachaty and Woerther, {Paul Louis} and G{\'e}rard Eberl and Marion B{\'e}rard and Chantal Ecobichon and Dominique Clermont and Chantal Bizet and Val{\'e}rie Gaboriau-Routhiau and Nadine Cerf-Bensussan and Paule Opolon and Nadia Yessaad and Eric Vivier and Bernhard Ryffel and Elson, {Charles O.} and Jo{\"e}l Dor{\'e} and Guido Kroemer and Patricia Lepage and Boneca, {Ivo Gomperts} and Fran{\c c}ois Ghiringhelli and Laurence Zitvogel",

year = "2013",

month = jan,

day = "1",

doi = "10.1126/science.1240537",

language = "English",

volume = "342",

pages = "971--976",

journal = "Science",

issn = "0036-8075",

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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, Numéro 6161, p. 971-976. https://doi.org/10.1126/science.1240537

TY - JOUR

T1 - The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide

AU - Viaud, Sophie

AU - Saccheri, Fabiana

AU - Mignot, Grégoire

AU - Yamazaki, Takahiro

AU - Daillère, Romain

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

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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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U2 - 10.1126/science.1240537

DO - 10.1126/science.1240537

M3 - Article

C2 - 24264990

AN - SCOPUS:84888059687

SN - 0036-8075

VL - 342

SP - 971

EP - 976

JO - Science

JF - Science

IS - 6161

ER -