Therapeutic Targeting of the IL-22/IL-22Rα Axis to Suppress Tumor Proliferation in Gynecologic Cancers 2330046

Abstract

Abstract Introduction This study explores the potential of Interleukin-22 receptor alpha (IL-22Rα) as a therapeutic target for gynecologic cancer. Gynecologic cancers, including cervical cancer and ovarian cancer, are closely associated with chronic inflammation. Interleukin (IL)-22, a pro-inflammatory cytokine involved in epithelial regeneration, has emerged as a critical mediator linking inflammatory signaling to oncogenic processes. Methods We investigated the functional role of IL-22/IL-22Rα signaling in cervical and ovarian cancer models by CCK-8 assay, cell cycle analysis, and Western blotting. Furthermore, IL-22Rα–knockdown cell lines were established to determine whether the proliferative effects were specifically mediated through IL-22/IL-22Rα signaling. Results IL-22 stimulation enhanced proliferation of cervical cancer cell lines (CaSki and HeLa) and ovarian cancer cell lines (SK-OV-3 and NIH:OVCAR-3) by promoting S and G2/M phase progression. This effect was accompanied by upregulation of cell cycle–associated cyclins, including A, B1, D1, and E1, without distinct changes in cyclin–dependent kinase expressions. Genetic suppression of IL-22Rα abrogated IL-22–induced signaling activation, cell cycle progression, and proliferation in vitro. Consistently, IL-22Rα suppression markedly inhibited IL-22–driven tumor growth in cervical cancer and ovarian cancer xenograft models. Conclusion Our findings identify the IL-22/IL-22Rα axis as a key inflammation–driven regulator of tumor proliferation in gynecologic cancers and reveal the potential therapeutic target of IL-22Rα. Funding Source n/a Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)