The Intestinal Microbiota Modulates the Anticancer Immune Effects of Cyclophosphamide

Science. 2013 Nov 22;342(6161):971-6. doi: 10.1126/science.1240537.

Abstract

Cyclophosphamide is one of several clinically important cancer drugs whose therapeutic efficacy is due in part to their ability to stimulate antitumor immune responses. Studying mouse models, we demonstrate that cyclophosphamide alters the composition of microbiota in the small intestine and induces the translocation of selected species of Gram-positive bacteria into secondary lymphoid organs. There, these bacteria stimulate the generation of a specific subset of "pathogenic" T helper 17 (pT(H)17) cells and memory T(H)1 immune responses. Tumor-bearing mice that were germ-free or that had been treated with antibiotics to kill Gram-positive bacteria showed a reduction in pT(H)17 responses, and their tumors were resistant to cyclophosphamide. Adoptive transfer of pT(H)17 cells partially restored the antitumor efficacy of cyclophosphamide. These results suggest that the gut microbiota help shape the anticancer immune response.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Bacterial Translocation / drug effects*
  • Cyclophosphamide / therapeutic use*
  • Germ-Free Life
  • Gram-Positive Bacteria / drug effects
  • Gram-Positive Bacteria / physiology
  • Immunologic Memory
  • Immunosuppressive Agents / therapeutic use*
  • Intestine, Small / microbiology*
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / microbiology
  • Mice
  • Microbiota / drug effects
  • Microbiota / physiology*
  • Neoplasms / drug therapy*
  • Neoplasms / immunology*
  • Th17 Cells / immunology
  • Th17 Cells / transplantation

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Immunosuppressive Agents
  • Cyclophosphamide