Deciphering the Adaptive Immune Response to Ovarian Cancer

Abstract : The presence of CD8+ tumor-infiltrating lymphocytes (CD8+ TIL) has been associated with increased patient survival in ovarian cancer. We discovered that this effect is even stronger when CD8+ TIL are found together with CD20+ B cells and CD4+FoxP3+ T cells. We hypothesized that CD20+ TIL contribute to tumor immunity by presenting antigens to CD4+ and CD8+ TIL. This year, we discovered that the major antibody-producing cells in ovarian cancer are not CD20+ TIL but plasma cells, therefore our immunoglobulin cloning efforts are being directed toward these cells. We also discovered an unexpectedly high diversity of T cell receptors (TCR) among tumor-infiltrating T cells, which has prompted us to develop a new high throughput method for T cell antigen discovery. Finally, we discovered a novel subset of CD4+ T cells that is strongly associated with patient survival and will be the focus of future antigen identification efforts. Overall, this project is progressing on schedule and is yielding innovative methods and publishable results that lead toward a better understanding of the immune response to ovarian cancer.