Enterococcus hirae and Barnesiella intestinihominis Facilitate Cyclophosphamide-Induced Therapeutic Immunomodulatory Effects

被引：660

作者：

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

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

Waldschmitt, Nadine ^{[4
]}

Yamazaki, Takahiro ^{[1
,2
]}

Isnard, Christophe ^{[5
,6
]}

Poirier-Colame, Vichnou ^{[1
,2
,3
]}

Duong, Connie P. M. ^{[1
,2
,7
]}

Flament, Caroline ^{[1
,2
,7
]}

Lepage, Patricia ^{[8
]}

Roberti, Maria Paula ^{[1
,2
,7
]}

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

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

Apetoh, Lionel ^{[9
,10
,11
]}

Becharef, Sonia ^{[1
,2
,7
]}

Rusakiewicz, Sylvie ^{[1
,2
,7
]}

Langella, Philippe ^{[8
]}

Sokol, Harry ^{[8
,12
,13
]}

Kroemer, Guido ^{[14
,15
,16
,17
,18
,19
]}

Enot, David ^{[1
,15
]}

Roux, Antoine ^{[1
,2
,3
,8
,18
]}

Eggermont, Alexander ^{[1
,3
]}

Tartour, Eric ^{[20
,21
]}

Johannes, Ludger ^{[22
,23
,24
]}

Woerther, Paul-Louis ^{[25
]}

Chachaty, Elisabeth ^{[25
]}

Soria, Jean-Charles ^{[1
,3
]}

Golden, Encouse ^{[26
]}

Formenti, Silvia ^{[26
]}

Plebanski, Magdalena ^{[27
]}

Madondo, Mutsa ^{[27
]}

Rosenstiel, Philip ^{[28
,29
]}

Raoult, Didier ^{[30
]}

Cattoir, Vincent ^{[5
,6
,31
]}

Boneca, Ivo Gomperts ^{[32
]}

Chamaillard, Mathias ^{[4
]}

Zitvogel, Laurence ^{[1
,2
,3
,7
]}

机构：

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

[2] GRCC, INSERM, U1015, F-94805 Villejuif, France

[3] Univ Paris Saclay, F-94270 Le Kremlin Bicetre, France

[4] Univ Lille, INSERM, Inst Pasteur Lille, CNRS,CHRU Lille,U1019,UMR 8204,CIIL, F-59000 Lille, France

[5] Univ Caen Basse Normandie, EA4655, U2RM, Equipe Antibioresistance, F-14033 Caen, France

[6] CHU Caen, Microbiol Serv, F-14033 Caen, France

[7] Ctr Clin Invest Biotherapies Canc CICBT 1428, F-94805 Villejuif, France

[8] Univ Paris Saclay, AgroParisTech, INRA, Micalis Inst, F-78350 Jouy En Josas, France

[9] INSERM, U866, Canc, Lipids,Nutr, F-21078 Dijon, France

[10] Univ Bourgogne Franche Comte, Dept Med, F-21078 Dijon, France

[11] Ctr Georges Francois Leclerc, Dept Oncol, F-21000 Dijon, France

[12] UPMC, Fac Med, AVENIR Team Gut Microbiota & Immun, ERL,INSERM,U 1157,UMR 7203, F-75012 Paris, France

[13] Hop St Antoine, AP HP, Serv Gastroenterol, F-75012 Paris, France

[14] INSERM, U848, F-94805 Villejuif, France

[15] Inst Gustave Roussy, Metabol Platform, F-94805 Villejuif, France

[16] INSERM, Ctr Rech Cordeliers, Equipe Labellisee Ligue Canc 11, U 1138, F-75006 Paris, France

[17] Hop Europeen Georges Pompidou, AP HP, Pole Biol, F-75015 Paris, France

[18] Univ Paris 05, Sorbonne Paris Cite, F-75006 Paris, France

[19] Karolinska Inst, Dept Womens & Childrens Hlth, Karolinska Univ Hosp, S-17176 Stockholm, Sweden

[20] Univ Paris 05, Sorbonne Paris Cite, Paris Cardiovasc Res Ctr, INSERM,U970, F-75015 Paris, France

[21] Hop Europeen Georges Pompidou, Serv Immunol Biol, F-75015 Paris, France

[22] INSERM, U1143, F-75005 Paris, France

[23] PSL Res Univ, Inst Curie, Endocyt Trafficking & Therapeut Delivery Grp, F-75248 Paris, France

[24] CNRS, UMR 3666, F-75005 Paris, France

[25] GRCC, Microbiol Serv, F-94805 Villejuif, France

[26] Weill Cornell Med, Dept Radiat Oncol, New York, NY USA

[27] Monash Univ, Dept Immunol & Pathol, Alfred Hosp Precinct, Prahran, Vic 3181, Australia

[28] Univ Kiel, Inst Clin Mol Biol, Campus Kiel, D-24105 Kiel, Germany

[29] Univ Hosp Schleswig Holstein, Campus Kiel, D-24105 Kiel, Germany

[30] AIX MARSEILLE UNIV, UMR 7278, URMITE Unite Rech Malad Infect & Trop Emergentes, INSERM 1095,IRD 198,Fac Med, F-13005 Marseille, France

[31] CNR Resistance Antibiot, Lab Associe Enterocoques, F-14033 Caen, France

[32] Inst Pasteur, Unit Biol & Genet Bacterial Cell Wall, F-75015 Paris, France

来源：

IMMUNITY | 2016年 / 45卷 / 04期

基金：

澳大利亚国家健康与医学研究理事会; 欧洲研究理事会;

关键词：

INTESTINAL MICROBIOTA; DENDRITIC CELLS; TRANSLOCATION; BLOCKADE; CANCER;

D O I：

10.1016/j.immuni.2016.09.009

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The efficacy of the anti-cancer immunomodulatory agent cyclophosphamide (CTX) relies on intestinal bacteria. How and which relevant bacterial species are involved in tumor immunosurveillance, and their mechanism of action are unclear. Here, we identified two bacterial species, Enterococcus hirae and Barnesiella intestinihominis that are involved during CTX therapy. Whereas E. hirae translocated from the small intestine to secondary lymphoid organs and increased the intratumoral CD8/ Treg ratio, B. intestinihominis accumulated in the colon and promoted the infiltration of IFN-gamma-producing gamma delta Tau cells in cancer lesions. The immune sensor, NOD2, limited CTX-induced cancer immunosurveillance and the bioactivity of these microbes. Finally, E. hirae and B. intestinihominis specific-memory Th1 cell immune responses selectively predicted longer progression-free survival in advanced lung and ovarian cancer patients treated with chemo-immunotherapy. Altogether, E. hirae and B. intestinihominis represent valuable ''oncomicrobiotics'' ameliorating the efficacy of the most common alkylating immunomodulatory compound.

引用

页码：931 / 943

页数：13

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