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01-01-2016 | Original Article

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

Authors: Mia Shapiro, Bisweswar Nandi, Christine Pai, Mehmet K. Samur, Dheeraj Pelluru, Mariateresa Fulciniti, Rao H. Prabhala, Nikhil C. Munshi, Jason S. Gold

Published in: Cancer Immunology, Immunotherapy | Issue 1/2016

Abstract

While inflammation has been associated with the development and progression of colorectal cancer, the exact role of the inflammatory Th17 pathway remains unclear. 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 APC^MIN/+ 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 APC^MIN/+ mouse model, despite the fact that helper T cells from RORγt-deficient APC^MIN/+ mice do not secrete IL-17A when subjected to Th17-polarizing conditions and that Il17a expression is decreased in the intestine of RORγt-deficient APC^MIN/+ mice. Differential expression of Th17-associated cytokines between IL-17A-deficient and RORγt-deficient APC^MIN/+ mice may explain the difference in adenoma development.

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Title: Deficiency of IL-17A, but not the prototypical Th17 transcription factor RORγt, decreases murine spontaneous intestinal tumorigenesis
Authors: Mia Shapiro
Bisweswar Nandi
Christine Pai
Mehmet K. Samur
Dheeraj Pelluru
Mariateresa Fulciniti
Rao H. Prabhala
Nikhil C. Munshi
Jason S. Gold
Publication date: 01-01-2016
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 1/2016
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-015-1769-2

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