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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

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

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