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

被引：2706

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

共 50 条

[21] A T cell repertoire timestamp is at the core of responsiveness to CTLA-4 blockade
Philip, Hagit
Snir, Tom
Gordin, Miri
Shugay, Mikhail
Zilberberg, Alona
Efroni, Sol
ISCIENCE, 2021, 24 (02)
[22] CD80 Expression on Tumor Cells Alters Tumor Microenvironment and Efficacy of Cancer Immunotherapy by CTLA-4 Blockade
Vackova, Julie
Polakova, Ingrid
Johari, Shweta Dilip
Smahel, Michal
CANCERS, 2021, 13 (08)
[23] A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C
Sangro, Bruno
Gomez-Martin, Carlos
de la Mata, Manuel
Inarrairaegui, Mercedes
Garralda, Elena
Barrera, Pilar
Ignacio Riezu-Boj, Jose
Larrea, Esther
Alfaro, Carlos
Sarobe, Pablo
Jose Lasarte, Juan
Perez-Gracia, Jose L.
Melero, Ignacio
Prieto, Jesus
JOURNAL OF HEPATOLOGY, 2013, 59 (01) : 81 - 88
[24] IDO blockade negatively regulates the CTLA-4 signaling in breast cancer cells
Azimnasab-Sorkhabi, Parviz
Soltani-Asl, Maryam
Yoshinaga, Tulio Teruo
Massoco, Cristina de Oliveira
Kfoury Junior, Jose Roberto
IMMUNOLOGIC RESEARCH, 2023, 71 (05) : 679 - 686
[25] The introduction of LAG-3 checkpoint blockade in melanoma: immunotherapy landscape beyond PD-1 and CTLA-4 inhibition
Kreidieh, Firas Y.
Tawbi, Hussein A.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY, 2023, 15
[26] Myeloid-derived suppressor cells and their role in CTLA-4 blockade therapy
de Coana, Yago Pico
Masucci, Giuseppe
Hansson, Johan
Kiessling, Rolf
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2014, 63 (09) : 977 - 983
[27] The CTLA-4 gene polymorphisms are associated with CTLA-4 protein expression levels in multiple sclerosis patients and with susceptibility to disease
Karabon, Lidia
Kosmaczewska, Agata
Bilinska, Malgorzata
Pawlak, Edyta
Ciszak, Lidia
Jedynak, Anna
Jonkisz, Anna
Noga, Leszek
Pokryszko-Dragan, Anna
Koszewicz, Magdalena
Frydecka, Irena
IMMUNOLOGY, 2009, 128 (01) : e787 - e796
[28] Patients with chronic lymphocytic leukaemia (CLL) differ in the pattern of CTLA-4 expression on CLL cells: the possible implications for immunotherapy with CTLA-4 blocking antibody
Ciszak, Lidia
Frydecka, Irena
Wolowiec, Dariusz
Szteblich, Aleksandra
Kosmaczewska, Agata
TUMOR BIOLOGY, 2016, 37 (03) : 4143 - 4157
[29] Impact of tumor localization on antitumor immunity with conditionally activated CTLA-4 blockade
Arias-Badia, Marcel
Pai, Chien-Chun Steven
Lwin, Yee May
Chen, Peixi
Srinath, Aahir
Tanaka, Miho
Musser, Emily
Goodearl, Andrew
Gorman, Jacob, V
Ritacco, Wendy
Fong, Lawrence
JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2025, 13 (04)
[30] Antitumor activity of epigenetic immunomodulation combined with CTLA-4 blockade in syngeneic mouse models
Covre, A.
Coral, S.
Nicolay, H.
Parisi, G.
Fazio, C.
Colizzi, F.
Fratta, E.
Di Giacomo, A. M.
Sigalotti, L.
Natali, P. G.
Maio, M.
ONCOIMMUNOLOGY, 2015, 4 (08):

← 1 2 3 4 5 →