Molecular analysis of IL-9 producing Th9 cells in the context of Colitis-associated cancer (CAC)

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In inflammatory bowel disease (IBD), there is an increased risk of developing colitis-associated colon carcinoma (CAC). In particular, increased rates of colorectal carcinoma in ulcerative colitis (CU) are known, depending on the site of manifestation and the extent of the inflammatory changes. In addition to disturbed intestinal homeostasis, cytokines that have proinflammatory and tumor-promoting effects are of crucial importance for carcinogenesis. CD4 + effector T cells that promote chronic inflammation through the production of proinflammatory cytokines in IBD create a tumor-appropriate environment that can lead to cancer initiation and progression. The exact mechanisms that links a long-lasting IBD with colorectal tumors, however, are so far largely unclear. Recently, we have been able to identify PU.1-expressing T cells, termed Th9 cells due to the production of the proinflammatory cytokine IL-9, which are important for inflammatory initiation in ulcerative colitis. At the same time, our findings suggest a tumor-promoting effect of IL-9 in experimental CAC, although the molecular mechanism of action that regulates carcinogenesis is still unclear. Therefore, the proposed project aims to investigate the functional importance of IL-9-producing Th9 cells in CAC in comparison to sporadic colorectal carcinoma through analyzes in experimental model systems and patient tissue.