Grant: Master's Award: Canada Graduate Scholarships

Ovarian cancer is among the most deadly cancers with a 5-year survival rate of 30-40%. Nonetheless, there is unequivocal evidence that patients who mount a strong immune response to their tumor experience significantly higher survival rates. The main cells that mediate this effect are T cells (a type of white blood cell). T cells recognize specific proteins, called antigens, which are present on the surface of tumor cells. An activated T cell can kill a tumor cell within minutes. However, there are two theoretical ways in which tumors can evade T cells. First, tumors can lose their antigens over time, dramatically reducing the ability of T cells to recognize and destroy them. Alternatively, tumors can broadly suppress T cell functional capacity and even induce T-cell death. Based on our preliminary studies, we hypothesize that the latter is true in most cases. To test this hypothesis, we will use state-of-the-art methods to produce an inventory of tumor-reactive T cells in primary and recurrent tumors from 10 ovarian cancer patients. Our hypothesis predicts that T cells harvested from primary tumors will recognize both primary and recurrent tumors. We further predict that T cells harvested from recurrent tumors will have lost the ability to recognize primary tumors due to either functional impairment or death of the tumor-reactive T cells. If our hypothesis proves correct, this will provide strong rationale for treating ovarian cancer patients with immune modulators, drugs that can prevent the functional impairment or death of T cells. Thus, this study will provide critical information for the rational use of immunotherapies for ovarian cancer and related malignancies.