Interleukin-17A is involved in enhancement of tumor progression in murine intestine

Immunobiology. 2012 Jan;217(1):54-60. doi: 10.1016/j.imbio.2011.08.002. Epub 2011 Sep 10.

Abstract

Interleukin (IL)-17A is a cytokine involved in neutrophilic inflammation but the role of IL-17A in anti-tumor immunity is controversial because both pro- and anti-tumor activities of IL-17A have been reported. We hypothesized that constitutive expression of IL-17A in intestinal environment modifies tumor growth. To address the issue, mice were inoculated into subserosa of cecum (i.c.) with murine EL4 lymphoma expressing a model tumor antigen, and tumor growth was monitored. IL-17A-producing cells were detected both in tumor mass and in normal intestinal tissue of i.c. tumor-bearing wild type mice. Tumor size in the wild-type mice was significantly higher than that in the cecum of IL-17A gene-knockout mice. Furthermore, anti-IL-17A monoclonal antibody treatment of wild-type mice resulted in decreased tumor size in the cecum. Model tumor-antigen-specific interferon-γ production was not modified in draining mesenteric lymph node cells in the absence or after neutralization of IL-17A. All the results suggest that constitutive expression of IL-17A in intestine enhances tumor growth, and anti-IL-17A antibody treatment is a candidate of a new anti-tumor immunotherapy against intestinal tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / administration & dosage*
  • Antibodies, Neutralizing / therapeutic use
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / immunology
  • Cecum / drug effects
  • Cecum / immunology*
  • Cecum / metabolism
  • Cecum / pathology
  • Gene Expression / immunology
  • Immunotherapy / methods*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Intestinal Neoplasms / drug therapy
  • Intestinal Neoplasms / immunology*
  • Intestinal Neoplasms / metabolism
  • Intestinal Neoplasms / pathology
  • Lymphoma / drug therapy
  • Lymphoma / immunology*
  • Lymphoma / metabolism
  • Lymphoma / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Serous Membrane / drug effects
  • Serous Membrane / immunology*
  • Serous Membrane / metabolism
  • Serous Membrane / pathology
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Neutralizing
  • Biomarkers, Tumor
  • Interleukin-17
  • Interferon-gamma