Gut Microbiome Modulates Response to anti-PD-1 Immunotherapy in Melanoma Patients

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Fecal Microbiota Transplantation
  • Gastrointestinal Microbiome / genetics
  • Gastrointestinal Microbiome / immunology*
  • Humans
  • Immunotherapy*
  • Melanoma / immunology
  • Melanoma / therapy*
  • Metagenome
  • Mice
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / therapy*

Substances

  • Programmed Cell Death 1 Receptor