Ovarian cancer affects approximately 1,700 women per year in Canada. Current treatment involves surgery and chemotherapy, which is initially effective in most cases. However, most patients relapse with chemotherapy-resistant tumors within a few years of treatment; this highlights the urgency for new, effective treatment strategies. Encouragingly, the immune system has a strong influence on survival in ovarian cancer. Tumors that are densely infiltrated by T cells (a type of immune cell) are linked to improved prognosis. However, a large proportion of patients lack dense T cell infiltrates. Instead, T cells are trapped in the surrounding stromal regions of the tumor and fail to make direct contact with tumor cells.
I hypothesize that the infiltration of T cells is inhibited by suppressive mechanisms in these stromal regions and with better understanding, these mechanisms can be reversed by immunotherapy. One objective of this project is to determine whether T cells that are trapped in stromal regions are capable of recognizing tumor cells. If so, then these T cells have the potential to recognize and eradicate tumors. Another objective is to identify and then block the signals by which stromal cells carry out suppressive functions. I will assess the effects on T cell infiltration and tumor regression following this blockade. This project will facilitate the development of new treatments that release T cells from the suppressive effects of stroma to launch more powerful attacks against ovarian cancer and related malignancies. The possibilities of using off-patent fibrosis drugs for cancer treatment will be investigated; this might result in an inexpensive, effective new form of immunotherapy, thus reducing costs and increasing the number of patients benefitting from these approaches. Since the BC Cancer Agency’s Deeley Research Centre (BCCA-DRC) is able to perform clinical trials, the work can be directly implicated into clinical research.
This research will be presented at both national and international conferences and published in international peer-reviewed journals. The BCCA-DRC’s clinical trials program will also provide me with ongoing opportunities to speak to patient support groups, clinicians, and lay audiences at forums focused on education, awareness and philanthropy.