Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients

被引：3133

作者：

Gopalakrishnan, V. ^{[1
,2
]}

Spencer, C. N. ^{[2
,3
]}

Nezi, L. ^{[3
]}

Reuben, A. ^{[1
]}

Andrews, M. C. ^{[1
]}

Karpinets, T. V. ^{[3
]}

Prieto, P. A. ^{[1
,20
]}

Vicente, D. ^{[1
]}

Hoffman, K. ^{[4
]}

Wei, S. C. ^{[5
]}

Cogdill, A. P. ^{[1
,5
]}

Zhao, L. ^{[3
]}

Hudgens, C. W. ^{[6
]}

Hutchinson, D. S. ^{[7
]}

Manzo, T. ^{[3
]}

de Macedo, M. Petaccia ^{[6
,21
]}

Cotechini, T. ^{[8
]}

Kumar, T. ^{[3
]}

Chen, W. S. ^{[9
]}

Reddy, S. M. ^{[10
]}

Sloane, R. Szczepaniak ^{[1
]}

Galloway-Pena, J. ^{[11
]}

Jiang, H. ^{[1
]}

Chen, P. L. ^{[9
,22
]}

Shpall, E. J. ^{[12
]}

Rezvani, K. ^{[12
]}

Alousi, A. M. ^{[12
]}

Chemaly, R. F. ^{[11
]}

Shelburne, S. ^{[3
,11
]}

Vence, L. M. ^{[5
]}

Okhuysen, P. C. ^{[11
]}

Jensen, V. B. ^{[13
]}

Swennes, A. G. ^{[7
]}

McAllister, F. ^{[14
]}

Sanchez, E. Marcelo Riquelme ^{[14
]}

Zhang, Y. ^{[14
]}

Le Chatelier, E. ^{[15
]}

Zitvogel, L. ^{[16
]}

Pons, N. ^{[15
]}

Austin-Breneman, J. L. ^{[1
,23
]}

Haydu, L. E. ^{[1
]}

Burton, E. M. ^{[1
]}

Gardner, J. M. ^{[1
]}

Sirmans, E. ^{[17
]}

Hu, J. ^{[18
]}

Lazar, A. J. ^{[6
,9
]}

Tsujikawa, T. ^{[8
]}

Diab, A. ^{[17
]}

Tawbi, H. ^{[17
]}

Glitza, I. C. ^{[17
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA

[2] Univ Texas Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA

[7] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA

[8] Oregon Hlth & Sci Univ, Dept Cell Dev & Cell Biol, Portland, OR 97239 USA

[9] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[10] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA

[11] Univ Texas MD Anderson Canc Ctr, Dept Infect Dis, Houston, TX 77030 USA

[12] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat, Houston, TX 77030 USA

[13] Univ Texas MD Anderson Canc Ctr, Dept Vet Med & Surg, Houston, TX 77030 USA

[14] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA

[15] Inst Natl Rech Agronom, Ctr Rech Jouy En Josas, F-78352 Jouy En Josas, France

[16] Inst Gustave Roussy, Ctr Invest Clin Biotherapie, F-94805 Villejuif, France

[17] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA

[18] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA

[19] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA

[20] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY 14642 USA

[21] AC Camargo Canc Ctr, Sao Paulo, Brazil

[22] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA

[23] Harvard Univ, Cambridge, MA 02138 USA

[24] MedImmune, Gaithersburg, MD 20878 USA

来源：

SCIENCE | 2018年 / 359卷 / 6371期

关键词：

INTESTINAL MICROBIOTA; CTLA-4; BLOCKADE; PD-1; CANCER; THERAPY; SENSITIVITY; MECHANISMS; IPILIMUMAB; DIVERSITY; NIVOLUMAB;

D O I：

10.1126/science.aan4236

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：

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.

引用

页码：97 / 103

页数：7

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