Grant: Doctoral Research Award: Canada Graduate Scholarships

The goal of cancer immunotherapy is to stimulate the immune system to recognize and destroy cancer cells. Ovarian cancer has remained largely resistant to today's immunotherapies, demonstrating that more work is needed to devise the optimal strategy to properly activate the immune system in this disease. Among the white blood cells, B cells are uniquely responsible for producing antibodies, proteins that specifically bind to foreign substances, pathogens, or other dangerous materials to neutralize them or flag them for destruction by other immune cells. The presence of B cells in tumors is associated with prolonged patient survival, yet we do not fully understand how B cells mediate this effect. To fill this knowledge gap and develop better immunotherapies, we will define the different types of B cells found in patient-derived ovarian tumor samples and determine what proteins their antibodies bind to enable recognition and killing of cancer cells. In Aim 1, we will employ sophisticated sequencing techniques to "read" molecular information from individual B cells and infer their functions based on the genes they express. This technique will also allow us to identify the antibodies that B cells use to recognize cancer cells. In Aim 2, we will determine which proteins B cells are recognizing on the surface of cancer cells, which may reveal new targets for immunotherapy. In Aim 3, we will determine the functions of B cell-derived antibodies by assessing their effects on immune cell activity and tumor cell death when added to cultures with these cells. By studying tumor-associated B cells at this high level of resolution, we will reveal for the first time how these cells facilitate the immune response against cancer. We may also identify new targets to incorporate into the next generation of immunotherapies relevant to ovarian cancer and other malignancies, leading to better outcomes for future cancer patients.