Grant: Operating Grant

It has recently been shown that many ovarian cancer patients mount immune responses against their tumor. This is reflected in the fact that many ovarian tumors are densely packed with "T cells", a type of white blood cell that fights viral and bacterial infections, as well as cancer. Importantly, patients with large numbers of T cells in their tumor live longer after chemotherapy compared to patients with fewer T cells in their tumor. However, there are several different types of T cells, including "helper", "killer" and "regulatory" T cells, and it is not clear which of these T cell types is most important for promoting survival in ovarian cancer. It is also not clear how standard treatments for ovarian cancer (i.e., surgery and chemotherapy) affect T cell responses against the tumor. These are critical issues for the development of immune-based treatments for this disease. Based on recent studies from our lab, we hypothesize that the functional activity of two T cell types (CD8+ killer T cells and FoxP3+ T cells) is a critical determinant of clinical outcomes in ovarian cancer. To investigate this hypothesis, we propose the following specific aims: Aim 1. To collect tumor-associated T cells and matched blood and tumor specimens from ovarian cancer patients. Aim 2. To define the functional properties of CD8+ and FoxP3+ T cells in ovarian cancer. Aim 3. To assess the effects of standard treatment on the functional properties of tumor-associated T cells in ovarian cancer. Aim 4. To determine the effect of FoxP3+ T cells on CD8+ T cell responses to ovarian cancer in a mouse model. With a better understanding of how standard treatments for ovarian cancer affect the immune system, we believe it will be possible in future to improve clinical outcomes further by enhancing the immune response using drugs, vaccines or T cell infusions.