Vitamin D regulates microbiome-dependent cancer immunity

Science. 2024 Apr 26;384(6694):428-437. doi: 10.1126/science.adh7954. Epub 2024 Apr 25.

Abstract

A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D-induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival. In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of Bacteroides fragilis, which positively regulates cancer immunity. Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer. Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.

Publication types

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

MeSH terms

  • Animals
  • Bacteroides fragilis* / metabolism
  • Calcifediol / administration & dosage
  • Calcifediol / metabolism
  • Cell Line, Tumor
  • Diet
  • Female
  • Gastrointestinal Microbiome* / drug effects
  • Humans
  • Immune Checkpoint Inhibitors* / pharmacology
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Immunotherapy
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms* / immunology
  • Neoplasms* / microbiology
  • Neoplasms* / therapy
  • Vitamin D* / administration & dosage
  • Vitamin D* / metabolism
  • Vitamin D-Binding Protein / genetics
  • Vitamin D-Binding Protein / metabolism

Substances

  • Immune Checkpoint Inhibitors
  • Vitamin D
  • Calcifediol
  • Vitamin D-Binding Protein