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Science. 2018 Jan 5;359(6371):97-103. doi: 10.1126/science.aan4236. Epub 2017 Nov 2.

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

Author information

1
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
2
Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, TX 77030, USA.
3
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
4
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
5
Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
6
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
7
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
8
Department of Cell, Developmental and Cell Biology, Oregon Health and Sciences University, Portland, OR 97239, USA.
9
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
10
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
11
Department of Infectious Diseases, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
12
Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
13
Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
14
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
15
Centre de Recherche de Jouy-en-Josas, Institut National de la Recherche Agronomique, 78352 Jouy-en-Josas, France.
16
Centre d'Investigation Clinique Biothérapie, Institut Gustave-Roussy, 94805 Villejuif Cedex, France.
17
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
18
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
19
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
20
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. jwargo@mdanderson.org.

Abstract

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.

Comment in

PMID:
29097493
PMCID:
PMC5827966
DOI:
10.1126/science.aan4236
[Indexed for MEDLINE]
Free PMC Article

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