Ovarian Cancer Immunotherapy en Route: IL9 Inhibits Growth of Ovarian Cancer and Upregulates its Expression of Ox40L and 4-1BBL

Abstract

Objective: Ovarian cancer is the deadliest of all gynecologic tumors. Current treatment methods include debulking surgery with chemotherapy, however even with treatment, the five-year survival rate is below 45%. Cancer immunotherapy is an innovative treatment option being highly researched. Interleukins (ILs) are signaling molecules used by the human immune system to assist in detecting and destroying cancer cells. The ability of tumor cells to evade the immune system is a major challenge we face in fighting cancer. Ox40L/Ox40 and 4-1BBL/4-1BB are key immune costimulatory molecules that increase T cell activation to eliminate tumors. Past research has shown that IL9 has unique influences on various types of cancer, however, its role in ovarian cancer has not yet been assessed. In this study, ovarian cancer cells were treated with IL9 and the expression of Ox40L and 4-1BBL were measured. Methods: A2780 ovarian cancer cells were treated with IL9. Proliferation of ovarian cancer cells was measured by a Clonogenic Survival Assay and Quick Proliferation Assay. RT-PCR was conducted to determine whether IL9 upregulated the costimulatory molecules Ox40L and 4-1BBL. IHC was performed to further investigate IL9 upregulation of Ox40L and 4-1BBL. Results: Treatment of A2780 ovarian cancer cells with IL9 resulted in decreased proliferation of the ovarian cancer cells. By using RT-PCR, it was determined that IL9 treated ovarian cancer cells displayed upregulation of the costimulatory molecules Ox40L and 4-1BBL. Upregulation of OX40L and 4-1BBL was further confirmed by IHC. Conclusions: IL9 inhibited growth of ovarian cancer cells, and IL9 upregulated the key immune costimulatory molecules Ox40L and 4-1BBL. This suggests that increased expression of Ox40L and 4-1BBL may be associated with the inhibitory effect of IL9 on proliferation of ovarian cancer. This study warrants further investigation of the role of Ox40L and 4-1BBL in ovarian cancer growth.