My graduate studies and postdoctoral training have spanned basic T-cell immunology research and translational and clinical research focused on improving T-cell based immunotherapies for patients with metastatic cancer. These experiences have given me a deep appreciation for the importance of basic research as well as an understanding of the challenges and complexities of designing novel immunotherapies for the treatment of patients with cancer. I was the lead scientific investigator in a clinical trial that tested whether the adoptive transfer of tumor infiltrating lymphocytes (TILs) could mediate tumor regression in patients with metastatic gastrointestinal (GI) cancers. Our collective experience in adoptive cell therapy (ACT) against melanoma suggested that T cells targeting neoantigens arising as a consequence of random somatic cancer mutations were the key mediators in the dramatic anti-tumor activity observed in some patients with melanoma. This led us to test whether neoantigen-reactive T cells could be found in patients with metastatic GI cancers, and more importantly, whether we could effectively harness the neoantigen-specific T-cell response to treat patients with GI cancers. To this end, I helped develop some of the first next-generation sequencing based experimental procedures that allowed us to evaluate whether T cells recognized mutated neoantigens expressed by the patient’s own tumor. I was also directly involved with carrying out and overseeing the assays that would ultimately determine whether the patient was treated. My training environment was truly “bench to bedside” as the experiments that we developed and carried out in the lab directly translated to patient treatment. Being able to witness the basic discovery that T cells recognizing neoantigens could be found in patients with GI cancers, and to see this translated to a patient treatment was a unique and rewarding experience. In some patients, tumor regression was observed after transfer of enriched populations of T cells targeting neoantigens, but many patients still succumbed to their disease after treatment and thus there is much work to be done to improve the efficacy of T-cell based therapies against metastatic cancers. My overlapping goals are to: 1) explore the mechanisms underlying the lack of anti-tumor efficacy in cancer patients following immunotherapy; and 2) develop more effective adoptive T-cell transfer therapies against common epithelial cancers.