Deficiency of IL-17A, but not the prototypical Th17 transcription factor RORγt, decreases murine spontaneous intestinal tumorigenesis

In this study, we aimed to determine the relative importance of IL-17A and the master regulator of the Th17 pathway, the transcription factor RORγt, in the sporadic intestinal neoplasia of APCMIN/+ mice and in human colorectal cancer. We show that levels of IL-17A are increased in human colon cancer as compared to adjacent uninvolved colon. Similarly, naïve helper T cells from colorectal cancer patients are more inducible into the Th17 pathway. Furthermore, IL-17A, IL-21, IL-22, and IL-23 are all demonstrated to be directly mitogenic to human colorectal cancer cell lines. Nevertheless, deficiency of IL-17A but not RORγt is associated with decreased spontaneous intestinal tumorigenesis in the APCMIN/+ mouse model, despite the fact that helper T cells from RORγt-deficient APCMIN/+ mice do not secrete IL-17A when subjected to Th17-polarizing conditions and that Il17a expression is decreased in the intestine of RORγt-deficient APCMIN/+ mice. Differential expression of Th17-associated cytokines between IL-17A-deficient and RORγt-deficient APCMIN/+ mice may explain the difference in adenoma development.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research