Grant: Master's Award: Canada Graduate Scholarships

Ovarian cancer affects over 1 in 100 women in Canada and has unacceptably high mortality rates. Despite this, about 15% of patients survive for 10 or more years after initial treatment. What makes these patients do so well? It has been established that many long-term survivors of ovarian cancer have immune cells in their tumours. These immune cells appear to be attacking the cancer cells, but the mechanisms by which they kill tumours remain largely unknown. Our lab is exploring how one such type of immune cell, called tumour-infiltrating B lymphocytes (TIL-B), recognize and attack tumours. B cells can contribute to immune responses by secreting antibodies which bind to diseased cells and tag them for destruction by a powerful immune mechanism called complement. Complement is a group of blood proteins that, when activated, bind to and rapidly destroy diseased cells. My research will assess whether TIL-B use complement to control tumours, particularly in long-term survivors of ovarian cancer. In Aim 1, the complement activity of TIL-B antibodies will be assessed by evaluating cancer cell viability and complement fragments on the cancer cell surface. In Aim 2, patient tumour samples will be assessed by immunofluorescent imaging which allows visualization of key steps in the complement pathway. These analyses will be the first - for any human cancer - to assess whether TIL-B antibodies activate complement. Additionally, comparing complement activation in tumours from long- and average-term survivors will uncover the role of this pathway in promoting patient survival. This work will inform new approaches to boost the immune response to ovarian cancer and related malignancies by enhancing the coordinated activity of TIL-B cells, their antibodies, and the complement pathway.