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

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.