Journal
SCIENCE
Volume 359, Issue 6371, Pages 97-103Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aan4236
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Funding
- Binational Science Foundation
- Melanoma Research Alliance
- Stand Up To Cancer
- MD Anderson Cancer Center Multidisciplinary Research Program Grant
- MD Anderson Cancer Center's Melanoma Moon Shots Program
- philanthropic
- Kimberley Clarke Foundation Award for Scientific Achievement by Odyssey Fellowship program at The University of Texas MD Anderson Cancer Center
- National Cancer Institute (NCI) of NIH [CA016672, R25CA057730]
- University of Texas MD Anderson Cancer Center's Various Donors Melanoma and Skin Cancers Priority Program Fund
- Stand Up To Cancer-Lustgarten Foundation Pancreatic Cancer Convergence Dream Team Translational Research Grant
- NCI of NIH
- Brenden-Colson Center for Pancreatic Health
- Oregon Clinical and Translational Research Institute from the National Center for Advancing Translational Sciences at the NIH (NIH) [UL1TR000128]
- GlaxoSmithKline
- Roche/Genentech
- Merck
- AstraZeneca
- Sanofi-Aventis
- AstraZeneca/MedImmune
- Novartis
- Bristol-Myers Squibb
- Grants-in-Aid for Scientific Research [17H07016] Funding Source: KAKEN
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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.
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