Project 463163

One population of white blood cells, called T cells, is known to have the ability to kill tumor cells. Clinical studies have shown that augmenting the function of these T cells using a particular antibody drug that targets a molecule called PD-1 is an extremely effective treatment for many patients. One cancer that responds well to this immunomodulatory drug is metastatic melanoma while another cancer that does not respond well is ovarian cancer. We have studied the T cells directly from melanoma and ovarian cancer. The markers displayed on these T cells in the melanoma group are similar, and the markers displayed on the T cells in ovarian cancer group are similar. However, these markers are very different if we compare the melanoma and ovarian cancer groups. This suggests that different properties of T cells are reflected by the markers that the T cells express, and it is different between the two cancers. In this proposal, we want to understand what the differences in these markers mean in terms of the biology and function of the T cells, and gain insights into the ability of the different cancers to respond to therapy. This understanding in fundamental biology may provide a guide to predict which patients will respond to therapy and how to improve therapy for other patients.