Grant: CIHR Fellowship

I aim to find strategies to overcome immune suppression in the tumor environment of ovarian cancer in order to create more effective immune-based treatments for patients. Current treatments for ovarian cancer, consisting of surgery and chemotherapy, are initially effective in most cases. However, most patients develop chemotherapy-resistant relapses, resulting in an unacceptably low survival rate of about 30% at 5 years. Encouragingly, the immune system has a strong influence on survival in ovarian cancer. Tumors that have a dense infiltration of T cells (a type of immune cell) are correlated with a markedly higher survival rate. However, a significant proportion of patients lack these 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 suppressive mechanisms inhibit the infiltration of T cells in these stromal areas and that, with better understanding, these mechanisms can be reversed by immunotherapy. In Aim 1, I will determine whether T cells that are trapped in stromal regions are nonetheless capable of recognizing tumor cells. If so, then these T cells have the potential to recognize and eradicate tumors. In Aim 2, I will attempt 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. 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.