Grant: Project Grant

Defining the problem. Ovarian Cancer (OVCA) ranks third in the number of new cases and is the leading cause of death in gynecologic cancer. Although combined surgical debulking and chemotherapy is an important treatment strategy, chemoresistance remains a major challenge to long term therapeutic success. There is currently no safe and successful therapy available once chemoresistance has developed. Recent studies indicate the tumour microenvironment as a strong contributing factor for chemoresistance. The microenvironment entails various cell types, including tumour cells and immune cells [e.g. T lymphocytes (T cells)], which communicate via cross-talks and local release of pro-cancer soluble factors. The overall objective of the proposed study is to determine if and how OVCA cells-T cells interactions regulate chemosensitivity and how deregulation of these interactions results in chemoresistance. The overall hypothesis is that OVCA cells-T cells interaction regulates OVCA CDDP responsiveness. A secreted protein called plasma gelsolin (pGSN) promotes cancer cell survival by down-regulating the anti-tumour functions of T cells. Clinical significance. Results from the proposed study could provide guidance to physicians on treatment strategies, particularly for platinum-based chemotherapy. The clinical management of OVCA patients may be individualized to achieve more benefits, especially avoiding treatment side effects in non-responders. In addition, the immune-modulatory role of pGSN may provide insight for future investigations on new immunotherapeutic for chemoresistant OVCA patients.