The Intestinal Microbiota Modulates the Anticancer Immune Effects of Cyclophosphamide

被引：1577

作者：

Viaud, Sophie ^{[1
,3
]}

Saccheri, Fabiana ^{[1
]}

Mignot, Gregoire ^{[4
,5
]}

Yamazaki, Takahiro ^{[1
]}

Daillere, Romain ^{[1
,3
]}

Hannani, Dalil ^{[1
]}

Enot, David P. ^{[7
,8
]}

Pfirschke, Christina ^{[9
,10
]}

Engblom, Camilla ^{[9
,10
]}

Pittet, Mikael J. ^{[9
,10
]}

Schlitzer, Andreas ^{[11
]}

Ginhoux, Florent ^{[11
]}

Apetoh, Lionel ^{[4
,5
]}

Chachaty, Elisabeth ^{[12
]}

Woerther, Paul-Louis ^{[12
]}

Eberl, Gerard ^{[13
]}

Berard, Marion ^{[14
]}

Ecobichon, Chantal ^{[15
,16
]}

Clermont, Dominique ^{[17
]}

Bizet, Chantal ^{[17
]}

Gaboriau-Routhiau, Valerie ^{[18
,19
]}

Cerf-Bensussan, Nadine ^{[18
,19
]}

Opolon, Paule ^{[20
,21
]}

Yessaad, Nadia ^{[22
,23
,24
,25
]}

Vivier, Eric ^{[22
,23
,24
,25
]}

Ryffel, Bernhard ^{[26
]}

Elson, Charles O. ^{[27
]}

Dore, Joel ^{[18
,28
]}

Kroemer, Guido ^{[7
,8
,29
,30
,31
]}

Lepage, Patricia ^{[18
,28
]}

Boneca, Ivo Gomperts ^{[15
,16
]}

Ghiringhelli, Francois ^{[4
,5
,6
]}

Zitvogel, Laurence ^{[1
,2
,3
]}

机构：

[1] INSERM, U1015, Equipe Labellisee Ligue Natl Canc, Inst Gustave Roussy, Villejuif, France

[2] Inst Gustave Roussy, Ctr Invest Clin Biotherapie, CICBT 507, Villejuif, France

[3] Univ Paris Sud, Le Kremlin Bicetre, France

[4] INSERM, U866, Ctr Georges Francois Leclerc, Dijon, France

[5] INSERM, Grp Avenir, Dijon, France

[6] Univ Bourgogne, Fac Med, Dijon, France

[7] Inst Gustave Roussy, INSERM, U848, F-94805 Villejuif, France

[8] Inst Gustave Roussy, Metab & Cell Biol, Villejuif, France

[9] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA

[10] Harvard Univ, Sch Med, Boston, MA USA

[11] ASTAR, Singapore Immunol Network SIgN Agcy Sci, Singapore, Singapore

[12] Inst Gustave Roussy, Microbiol Serv, Villejuif, France

[13] Inst Pasteur, Lymphoid Tissue Dev Unit, Paris, France

[14] Inst Pasteur, Animalerie Cent, Paris, France

[15] Inst Pasteur, Unit Biol & Genet Bacterial Cell Wall, Paris, France

[16] INSERM, Grp Avenir, Paris, France

[17] Inst Pasteur, Collect Inst Pasteur, Paris, France

[18] INRA, Micalis UMR1319, F-78350 Jouy En Josas, France

[19] Univ Paris 05, INSERM, U989, F-75730 Paris, France

[20] Inst Gustave Roussy, IFR54, Villejuif, France

[21] Inst Gustave Roussy, IRCIV, Lab Pathol Expt, Villejuif, France

[22] Aix Marseille Univ UM2, Ctr Immunol Marseille Luminy, Marseille, France

[23] INSERM, UMR 1104, F-13258 Marseille, France

[24] Ctr Natl Rech Sci, UMR 7280, Marseille, France

[25] Hop Conception, Assistance Publ Hop Marseille, Marseille, France

[26] Univ Orleans, CNRS, Lab Mol & Expt Immunol & Neurogenet, UMR 7355, Orleans, France

[27] Univ Alabama Birmingham, Birmingham, AL USA

[28] AgroParisTech, Micalis UMR1319, F-78352 Jouy En Josas, France

[29] Ctr Rech Cordeliers, Equipe Labellisee Ligue Canc 11, Paris, France

[30] Hop Europeen Georges Pompidou, AP HP, Pole Biol, Paris, France

[31] Univ Paris 05, Paris, France

来源：

SCIENCE | 2013年 / 342卷 / 6161期

基金：

欧洲研究理事会;

关键词：

BARRIER; CELLS;

D O I：

10.1126/science.1240537

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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(H)17) cells and memory T(H)1 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(H)17 responses, and their tumors were resistant to cyclophosphamide. Adoptive transfer of pT(H)17 cells partially restored the antitumor efficacy of cyclophosphamide. These results suggest that the gut microbiota help shape the anticancer immune response.

引用

页码：971 / 976

页数：6

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