Grant: Project Grant

Ovarian cancer is a challenging disease with unacceptably high mortality. Despite this, about 30% of patients "beat the odds" and live for many years after treatment. Why do some patients do so well? In the past decade, it has become well established that many long-term survivors of ovarian cancer spontaneously mount a strong immune response against their tumor, providing a compelling explanation for their favourable outcome. Building on this understanding, our team has shown that the immune response against cancer involves collaboration between several types of white blood cells, including T cells, B cells and macrophages, each of which has unique mechanisms for recognizing and killing tumour cells. With better understanding of the immune response, it will be possible to design new treatments that enhance tumor immunity and increase patient survival. In this study, we will investigate the mechanisms by which the above three cell types work together to recognize and attack cancer. In Aim 1, we will use state-of-the-art methods to visualize in two-dimensional space the molecular properties of individual T cells, B cells, macrophages and other immune cells in tumours from ovarian cancer patients. In Aim 2, we will use a groundbreaking new method pioneered by our team to decipher for the first time the spatial locations and collaborative interactions between hundreds of T cells and B cells in tumour specimens from patients. In Aim 3, we will interrogate our data to find new pathways that can be therapeutically targeted to enhance the immune response to ovarian cancer. The data, tools and knowledge arising from this study will help us design new immunotherapies that fortify the patient's natural defense mechanisms, leading to increased survival. Through local and national initiatives, our team is exceptionally well positioned to translate our findings into early stage clinical trials of promising new immunotherapy strategies for ovarian cancer patients in Canada.