Redundant Innate and Adaptive Sources of IL17 Production Drive Colon Tumorigenesis

Franck Housseau, Shaoguang Wu, Elizabeth C. Wick, Hongni Fan, Xinqun Wu, Nicolas J. Llosa, Kellie N. Smith, Ada Tam, Sudipto Ganguly, Jane W. Wanyiri, Thevambiga Iyadorai, Ausama A. Malik, April C. Roslani, Jamunarani S. Vadivelu, Sara Van Meerbeke, David L. Huso, Drew M. Pardoll, Cynthia L. Sears

Research output: Contribution to journalArticlepeer-review

Abstract

IL17-producing Th17 cells, generated through a STAT3-dependent mechanism, have been shown to promote carcinogenesis in many systems, including microbe-driven colon cancer. Additional sources of IL17, such as γδ T cells, become available under inflammatory conditions, but their contributions to cancer development are unclear. In this study, we modeled Th17-driven colon tumorigenesis by colonizing Min Apc+/-ice with the human gut bacterium, enterotoxigenic Bacteroides fragilis (ETBF), to investigate the link between inflammation and colorectal cancer. We found that ablating Th17 cells by knocking out Stat3 in CD4+T cells delayed tumorigenesis, but failed to suppress the eventual formation of colonic tumors. However, IL17 blockade significantly attenuated tumor formation, indicating a critical requirement for IL17 in tumorigenesis, but from a source other than Th17 cells. Notably, genetic ablation of gd T cells in ETBF-colonized Th17-deficient Min mice prevented the late emergence of colonic tumors. Taken together, these findings support a redundant role for adaptive Th17 cell- and innate gdT17 cell-derived IL17 in bacteria-induced colon carcinogenesis, stressing the importance of therapeutically targeting the cytokine itself rather than its cellular sources.

Original languageEnglish (US)
Pages (from-to)2115-2124
Number of pages10
JournalCancer Research
Volume76
Issue number8
DOIs
StatePublished - Apr 15 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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