Gut Microbiota Promotes Tumor Growth in Mice by Modulating Immune Response

Gastroenterology. 2018 Jul;155(1):33-37.e6. doi: 10.1053/j.gastro.2018.04.001. Epub 2018 Apr 7.

Abstract

We studied the effects of gut microbiome depletion by oral antibiotics on tumor growth in subcutaneous and liver metastases models of pancreatic cancer, colon cancer, and melanoma. Gut microbiome depletion significantly reduced tumor burden in all the models tested. However, depletion of gut microbiome did not reduce tumor growth in Rag1-knockout mice, which lack mature T and B cells. Flow cytometry analyses demonstrated that gut microbiome depletion led to significant increase in interferon gamma-producing T cells with corresponding decrease in interleukin 17A and interleukin 10-producing T cells. Our results suggest that gut microbiome modulation could emerge as a novel immunotherapeutic strategy.

Keywords: Gut Bacteria; Immune Regulation; Metastases; Tumor Promotion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Carcinoma / secondary
  • Cell Line, Tumor
  • Colonic Neoplasms / pathology
  • Disease Models, Animal
  • Dysbiosis / immunology*
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Microbiome / immunology*
  • Interferon-gamma / immunology
  • Interleukin-10 / immunology
  • Interleukin-17 / immunology
  • Liver Neoplasms / immunology
  • Liver Neoplasms / secondary
  • Melanoma / immunology
  • Melanoma / secondary
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / secondary
  • Mice
  • Mice, Knockout
  • Neoplasm Metastasis / immunology*
  • Neoplasm Transplantation
  • Neoplasms / immunology*
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / pathology
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • Soft Tissue Neoplasms / immunology
  • Soft Tissue Neoplasms / secondary
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes / immunology
  • Tumor Microenvironment / immunology

Substances

  • Anti-Bacterial Agents
  • IL10 protein, mouse
  • Il17a protein, mouse
  • Interleukin-17
  • Interleukin-10
  • Interferon-gamma