Commensal Bifidobacterium Promotes Antitumor Immunity and Facilitates anti-PD-L1 Efficacy

Science. 2015 Nov 27;350(6264):1084-9. doi: 10.1126/science.aac4255. Epub 2015 Nov 5.

Abstract

T cell infiltration of solid tumors is associated with favorable patient outcomes, yet the mechanisms underlying variable immune responses between individuals are not well understood. One possible modulator could be the intestinal microbiota. We compared melanoma growth in mice harboring distinct commensal microbiota and observed differences in spontaneous antitumor immunity, which were eliminated upon cohousing or after fecal transfer. Sequencing of the 16S ribosomal RNA identified Bifidobacterium as associated with the antitumor effects. Oral administration of Bifidobacterium alone improved tumor control to the same degree as programmed cell death protein 1 ligand 1 (PD-L1)-specific antibody therapy (checkpoint blockade), and combination treatment nearly abolished tumor outgrowth. Augmented dendritic cell function leading to enhanced CD8(+) T cell priming and accumulation in the tumor microenvironment mediated the effect. Our data suggest that manipulating the microbiota may modulate cancer immunotherapy.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • B7-H1 Antigen / immunology*
  • Bifidobacterium / genetics
  • Bifidobacterium / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Dendritic Cells / immunology
  • Fecal Microbiota Transplantation
  • Gastrointestinal Microbiome / immunology*
  • Gene Expression Regulation
  • Humans
  • Immunity / genetics
  • Immunotherapy / methods
  • Lymphocyte Activation
  • Melanoma / immunology*
  • Melanoma / therapy*
  • Mice
  • Mice, Inbred C57BL
  • RNA, Ribosomal, 16S / genetics
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / therapy*
  • Symbiosis
  • T-Lymphocytes / immunology
  • Tumor Microenvironment / immunology

Substances

  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • RNA, Ribosomal, 16S