Our ability to harness immune responses against cancer is one of the greatest medical advances of the past century. Nonetheless, most cancer patients are unresponsive to immunotherapy. Central to the immune response are T cells that can recognize tumor cells. These T cells express proteins called T cell receptors (TCRs) that specifically bind to other proteins expressed on tumor cells. Immunotherapies typically leverage T cells by one of two approaches: immune checkpoint inhibitors activate existing T cells to identify and kill tumors, while engineered cell therapies modify patient T cells so that they express a single tumor-specific TCR. When checkpoint inhibitors fail, it is likely because the correct T cells are not activated, and when engineered cell therapies fail it is likely due to their reliance upon a single TCR. Thus, identifying additional tumor-specific TCRs in patients could potentiate the engineered therapy approach. With the support of the SCI Innovation Award, Reticker-Flynn will develop a new platform that enables screening of millions of T cells from patients to identify additional tumor-specific TCRs. He will apply this technology to investigate TCRs in mouse models of metastatic cancer, and in patients with head and neck cancer, whose cancer has spread to lymph nodes. This work will lay a foundation for understanding immune responses to metastatic cancers and developing new T cell therapies.