Deciphering the Adaptive Immune Response to Ovarian Cancer
Technical Report,30 Sep 2012,29 Sep 2015
British Columbia Cancer Agency, Victoria BC V8R 6V5 Canada
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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. During the funding period, we discovered that the major antibody-producing cells in ovarian cancer are not CD20 TIL but plasma cells, therefore our immunoglobulin cloning efforts have been directed toward these cells. We also discovered an unexpectedly high diversity of T cell receptors TCR among tumor-infiltrating T cells, which 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 progressed on schedule and yielded innovative methods, multiple publications, and new funding sources, all of which will facilitate the development of more effective immunotherapies for ovarian cancer.