Interleukin-33 expression in ovarian cancer and its possible suppression of peritoneal carcinomatosis

Refractory peritoneal carcinomatosis is a common terminal feature of epithelial ovarian cancer (EOC). Previous reports have suggested that immunotherapy is a promising therapeutic strategy for EOC. Interleukin (IL)-33 is a member of the IL-1 superfamily of cytokines. The role of IL-33 in tissue inflammation and promoting type 2 immune responses has been established, and recently, there is accumulating evidence to suggest the involvement of IL-33 in carcinogenesis. In this study, we focused on the association between the tumor expression of IL-33 and ovarian peritoneal carcinomatosis. We used an immunosufficient murine model of peritoneal carcinomatosis and human EOC samples. The overexpression of IL-33 in the ID8 mouse EOC cell line tumors significantly prolonged the survival of immunocompetent mice in the peritoneal carcinomatosis setting, but not in the subcutaneous model. In addition, the silencing of IL-33 in ID8-T6 cells (subclone with high dissemination potential) significantly shortened the survival of the tumor-bearing mice. This was likely due to the intratumoral accumulation of CD8⁺ and CD4⁺ T cells, and a decrease in CD11b⁺Gr1⁺ cells. Furthermore, IL-33 induced the intraperitoneal microenvironment favoring tumor elimination through the inhibition of differentiation into CD11b⁺G r1⁺ cells. On the whole, the findings of this study suggest IL-33 to be a cytokine that reflects antitumor peritoneal conditions. Further investigation of the antitumorigenic role of IL-33 may aid in the development of more effective therapeutic approaches for the treatment of EOC with peritoneal carcinomatosis.