Abstract 3186: Role of Interleukin 1 signaling in tumor elicited inflammation and colon cancer

Abstract

Colorectal cancer (CRC) is the 2nd most common cause of cancer deaths in the United States and other developed countries, despite important advances in detection, surgery and chemotherapy. It becomes increasingly clear that not only cell autonomous events in cancer cells are required for tumor growth and progression. Growing CRC tumors possess the ability to recruit inflammatory cells and upregulate inflammatory cytokines - a phenomenon recently introduced as “Tumor elicited inflammation”(TEI). The mechanisms of TEI induction and tumor promotion are not yet well defined. IL23/IL17 pathway is one of the established regulators of TEI. While in mice the ablation of IL-23 signaling results in a uniform loss of IL-17 response and in a decrease in tumor growth; in humans IL23/IL-23R gene expression signature is not always consistent with elevated IL-17 signature, implicating that there should be other regulators of IL-17 and TEI induction in tumors. IL-1 pathway is important for the induction of T helper IL-17 producing cells (Th17) and for the production of IL-17 by innate lymphoid cells (ILC), both in mice and in humans. IL-1 pathway is also implicated in host defense, immunity and tumorigenesis, with some of its functional characteristics similar to IL-23 pathway. In addition, IL-1, much alike IL-23, can be also induced by various microbial derived and host derived ‘danger signals’ readily available within the tumor microenvironment. Our own data suggests that components of IL-1 pathway are upregulated in CRC tumors. Therefore, we hypothesized, that IL-1 pathway might be an important regulator of TEI and CRC tumorigenesis. Using genetic tools and animal models, we examined if IL-1 has the potential role in different stage of CRC and whether it serves as an important regulator of TEI and CRC tumor cells proliferation and survival. Citation Format: Oxana Dmitrieva, David Possoco, Ralph A. Francescone, Vivianty Hou, Debora B. Vendramini-Costa, Sergey Grivennikov. Role of Interleukin 1 signaling in tumor elicited inflammation and colon cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3186. doi:10.1158/1538-7445.AM2015-3186