Abstract 1421: Interleukin-22, a protective factor for ovarian cancer during TNFa-induced apoptosis.

Abstract

Abstract Ovarian cancer is the 5th leading cause of death from cancer in women. Overall, only 10% of patients with advanced ovarian cancer are curable; despite the advances in chemotherapy the 5-year survival is still less than 30%. Interleukin-22 (IL-22), a member of the IL-10 family of cytokines is part of the innate immune system and is expressed by the Th17 cells. IL-22 has been shown to regulate several processes such as the acute-phase response, activation of the innate immune system, cell migration, differentiation and gene expression. However, its role in cancer immunology, especially in ovarian cancer has not been studied. The aim of this study is to investigate the expression and the role IL-22 in human ovarian cancer. In our work, we analyzed the expression of IL-22 protein in human ovarian cancer tissues and ascites samples using immunohistochemistry and ELISA; we tested the expression of IL-22 receptor on human ovarian cancer cells via Western Blot, and determined the association between disease outcome and IL-22 gene expression (Affymetrix)in patients with human ovarian cancer. We evaluated the effect of IL-22 on cellular proliferation using MTT assay and we assessed the effect of IL-22 on TNF-a induced apoptosis using caspase 3/7 activity (Caspase Glo) assay and 7AAD staining on multiple human ovarian cancer cell lines. Here we demonstrate that IL-22 was expressed in human ovarian cancer tissue (mostly in the stroma) and that the receptor for IL-22 was expressed on human ovarian cancer cells. We found that high expression of IL-22, as well as the IL-22-receptor in the tumor tissue leads to poor disease outcome in ovarian cancer patients. On the contrary, high expression of IL-22-binding protein (antagonist of IL-22) was associated with better survival in ovarian cancer patients. We showed that treatment with human recombinant (hr) IL-22 protein induced the activation of Stat-3, as well as increased the proliferation of human ovarian cancer cell lines. We also found that treatment with hr IL-22 at 100, 50 or even at 10 ng/mL concentrations inhibited TNF-a induced apoptosis in OVCAR-5 ovarian cancer cell line, and these results were reversed by the addition of IL22 binding protein to the culture. We conclude that interleukin-22 is an important factor in the tumor microenvironment of ovarian cancer; it promotes tumor growth by increasing proliferation and serves as a protective factor for ovarian cancer during TNF-s induced apoptosis. These data suggest that IL-22 is a potential therapeutical target and/or biomarker in human ovarian cancer. Citation Format: Klara Balint, Tamara Seedial, Phyllis Gimotty, George Coukos, Andrea Facciabene. Interleukin-22, a protective factor for ovarian cancer during TNFa-induced apoptosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1421. doi:10.1158/1538-7445.AM2013-1421