Chronic inflammation in the intestine increases the risk of developing colorectal cancer. This becomes evident in patients with inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn's patients, who indeed have a higher probability of developing colitis-associated cancers. The main aim of the project is to control colorectal cancer development by targeting Th17 cells, a subset of CD4 T cells, which are fundamental in promoting chronic intestinal inflammation when they escape the physiological controls. By the combination of different cutting edges technologies, including fate-cytokine reporter mouse models and RNA seq., we found that formerly pro-inflammatory Th17 cells can convert into regulatory T cells (Tregs) and acquire a strong IL-10-mediated anti-inflammatory function (Gagliani N. et al.; Nature; 2015). Moreover we proved that Th17 cells infiltrate the intestinal tumors and produce IL-22, a cytokine known to be pro-tumorigenic (Unpublished data). Considering that (i) Th17 cells infiltrate and support tumor development, (ii) could be converted into Tregs and (iii) that IL-10 production it has been shown to have anti-tumorigenic effect, we are about to test whether by forcing the conversion of pro-tumrogienc Th17 into anti-tumorigenic regulatory T cells, it is possible to reduce intestinal tumor development in preclinical mouse models.
Citation Format: Nicola Gagliani, Carolina Amezcua Vasely, Hao Xu, Samuel Huber, Richard Flavell. Can the pro-tumorigenic activity of Th17 cells be a therapeutic opportunity? [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B088.
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