Grant: Operating 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 some ovarian cancer patients mount strong immune responses against their tumor. Tumors from such patients are densely packed with killer T cells, a type of white blood cell that fights viral and bacterial infections, as well as cancer. Importantly, patients with large numbers of killer T cells in their tumor have markedly higher survival rates. This is a very promising finding, as it shows that the immune system can have a profound influence on survival from ovarian cancer. With better understanding of the immune response, it will be possible to design new treatments such as vaccines that enhance tumor immunity and increase patient survival. However, to do this intelligently, we need to better understand how the immune response works. Although killer T cells are important for fighting tumors, they do not work alone. We recently showed that tumors containing both T cells and B cells are associated with even higher survival rates than seen with T cells alone. In this study, we will investigate the mechanisms by which T cells and B cells work together to promote tumor immunity. We will pay particular attention to how the immune system adapts to changes in the tumor during standard treatment and progression. We envision our work will lead to a major re-think about cancer immunotherapy: instead of simply trying to activate killer T cells, we also need to find effective ways to activate their team mates, the B cells. With better understanding of how T cells and B cells fight cancer, we can design new forms of treatment that enhance the patient's natural defences.