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

被引：2796

作者：

Vetizou, Marie ^{[1
,2
,3
]}

Pitt, Jonathan M. ^{[1
,2
,3
]}

Daillere, Romain ^{[1
,2
,3
]}

Lepage, Patricia ^{[4
]}

Waldschmitt, Nadine ^{[5
]}

Flament, Caroline ^{[1
,2
,6
]}

Rusakiewicz, Sylvie ^{[1
,2
,6
]}

Routy, Bertrand ^{[1
,2
,3
,6
]}

Roberti, Maria P. ^{[1
,2
,6
]}

Duong, Connie P. M. ^{[1
,2
,6
]}

Poirier-Colame, Vichnou ^{[1
,2
,6
]}

Roux, Antoine ^{[1
,2
,7
]}

Becharef, Sonia ^{[1
,2
,6
]}

Formenti, Silvia ^{[8
]}

Golden, Encouse ^{[8
]}

Cording, Sascha ^{[9
]}

Eberl, Gerard ^{[9
]}

Schlitzer, Andreas ^{[10
]}

Ginhoux, Florent ^{[10
]}

Mani, Sridhar ^{[11
,12
]}

Yamazaki, Takahiro ^{[1
,2
]}

Jacquelot, Nicolas ^{[1
,2
,3
]}

Enot, David P. ^{[1
,13
]}

Berard, Marion ^{[14
]}

Nigou, Jerome ^{[15
,16
]}

Opolon, Paule ^{[1
]}

Eggermont, Alexander ^{[1
,2
,17
]}

Woerther, Paul-Louis ^{[18
]}

Chachaty, Elisabeth ^{[18
]}

Chaput, Nathalie ^{[1
,19
]}

Robert, Caroline ^{[1
,20
]}

Mateus, Christina ^{[1
]}

Kroemer, Guido ^{[13
,21
,22
,23
]}

Raoult, Didier ^{[24
]}

Boneca, Ivo Gomperts ^{[25
,26
]}

Carbonnel, Franck ^{[27
]}

Chamaillard, Mathias

Zitvogel, Laurence ^{[1
,2
,3
,6
]}

机构：

[1] Inst Cancerol Gustave Roussy Canc Campus GRCC, 114 Rue Edouard, F-94805 Villejuif, France

[2] GRCC, INSERM, U1015, Villejuif, France

[3] Univ Paris Sud, Univ Paris 11, Le Kremlin Bicetre, France

[4] INRA, Micalis UMR1319, F-78360 Jouy En Josas, France

[5] Univ Lille, Ctr Hosp Reg Univ Lille, Inst Pasteur Lille,CNRS,INSERM, U1019,UMR 8204,Ctr Infect Immunite Lille CIIL, F-59000 Lille, France

[6] Ctr Clin Invest Biotherapies Canc 1428, Villejuif, France

[7] Univ Paris 05, Sorbonne Paris Cite, Paris, France

[8] NYU, Dept Radiat Oncol, New York, NY USA

[9] Inst Pasteur, Microenvironm & Immun Unit, Paris, France

[10] Agcy Sci Technol & Res, A STAR, Singapore Immunol Network SIgN, Singapore, Singapore

[11] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA

[12] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA

[13] GRCC, Metab Platform, Villejuif, France

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

[15] Inst Pharmacol & Biol Struct IPBS, CNRS, Toulouse, France

[16] Univ Paul Sabatier, Univ Toulouse, IPBS, F-31077 Toulouse, France

[17] Inst Gustave Roussy, Dept Med Oncol, Villejuif, France

[18] GRCC, Serv Microbiol, Villejuif, France

[19] GRCC, CNRS, INSERM, US 23,Lab Immunomonitoring Oncol,UMS 3655, Villejuif, France

[20] GRCC, INSERM, U981, Villejuif, France

[21] INSERM, U848, Villejuif, France

[22] Ctr Rech Cordeliers, Equipe Labellisee Ligue Natl Canc 11, INSERM, U1138, Paris, France

[23] Assistance Publ Hop Paris, Hop Europeen Georges Pom, Pole Biol, Paris, France

[24] Aix Marseille Univ, Univ Mediterranee, Fac Med, Unite Rickettsies, Marseille, France

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

[26] INSERM, Equipe Avenir, Paris, France

[27] Assistance Publ Hop Paris, Hop Bicetre, Dept Gastroenterol, Paris, France

来源：

SCIENCE | 2015年 / 350卷 / 6264期

基金：

欧洲研究理事会;

关键词：

T-CELLS; ANTIBODY; MOLECULE; CANCER; INNATE; MODEL;

D O I：

10.1126/science.aad1329

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：

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, Tcell 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.

引用

页码：1079 / +

页数：7

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