Ovarian carcinoma claims the lives of more than 14,000 American women every year. It is often detected at late stages and the standard treatment based on surgery and chemotherapy have met with very limited success during the past 40 years. Indeed, the 5-year overall survival rate for patients remains at less than 27%. Hence, there is an urgent need for the development of novel and more effective strategies to improve the current treatments for this disease.
Immune T cells possess the remarkable ability of recognizing and eliminating cancer cells. Immunotherapeutic strategies aimed at exploiting the anti-cancer capacity of T cells have shown impressive effects for the treatment of some tumor types, such as melanoma and lung carcinoma. However, the response rate of ovarian cancer patients to immunotherapy is marginal. One possible reason for this poor therapeutic response is the adverse environment of ovarian tumors, which inhibits the inherent protective function of immune cells. Therefore, identifying, understanding and targeting the specific pathways that ovarian tumors exploit in immune cells to control their activity is fundamental for developing the next generation of successful ovarian cancer immunotherapies.
Our laboratory pioneered the discovery that immune cells within ovarian tumors are “stressed out” within these malignant masses due to harsh environmental conditions such as decreased oxygen availability and lack of nutrients. The central hypothesis of our project is that stressed out immune cells in ovarian cancer are unable to execute their crucial anti-tumoral functions. Accordingly, this project will comprehensively characterize the tactics that ovarian cancers utilize to induce cellular stress in the immune system and will unveil the functional processes that are affected in stressed out immune cells. In addition, we will test the novel translational hypothesis that controlling immune stress within the tumor environment could be used as a new strategy to generate protective immunity against ovarian cancer. In summary, our project will provide novel mechanistic insights into how ovarian cancer manipulates the function of immune cells to evade immune control and will also establish first-in-class therapeutic interventions aimed at unleashing durable anti-ovarian cancer immunity.
This grant was made possible in part by a generous donation from Allison Danré, in honor of Cecile Hryhorczuk.