Abstract 2109: Prognostic and functional significance of interleukin 22 in colorectal cancer

Abstract

Abstract T cell infiltration has been recognized to significantly impact clinical outcome in human colorectal cancer (CRC). Interleukin 22 (IL-22), a cytokine secreted by IL-17-producing CD4+ T cells (Th17) is known to play a crucial role in inflammatory bowel disease and has been shown to have protumorigenic activity in mouse tumor models. However, its role in human CRC is still unclear. In a previous study we could demonstrate the dual role of Th17 in CRC. As consequence we evaluated the prognostic and functional impact of IL-22 producing cells in human CRC in this follow-up study. Upon staining of a tissue microarray (TMA), including 423 CRC cases, IL-22 positive cells were detected both within tumor cells and tumor infiltrating immune cells. Whereas, IL-22 expression by tumor cells did not impact on prognosis, densities of IL-22 positive immune cells were found to be significantly associated with early T stage and MMR-deficient microsatellite stability. Importantly, IL-22 expression by CRC infiltrating immune cells was predictive of improved overall survival independent of known prognostic factors such as T stage, N stage, tumor grade, vascular invasion, tumor border configuration and MMR status. Phenotypic characterization of IL-22 positive cells performed by flow cytometry revealed that they consist mainly of Th17 cells, also producing IL-17. In vitro experiments showed no direct effect of IL-22 on CRC cell proliferation. On-going studies are validating the prognostic effect on a TMA cohort with corresponding transcriptomic data and evaluating potential effects mediated by IL-22 on other cell types of CRC microenvironment. Citation Format: Eleonora Cremonesi, Nadia Tosti, Francesca Amicarella, Benjamin Weixler, Silvio Däster, Valeria Governa, Giulio C. Spagnoli, Luigi Terracciano, Luigi Tornillo, Serenella Eppenberger-Castori, Giandomenica Iezzi, Raoul Droeser. Prognostic and functional significance of interleukin 22 in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2109.