The general focus of the Brody Lab, a part of the Lymphoma Immunotherapy Program at The Tisch Cancer Institute at The Icahn School of Medicine at Mount Sinai, is the use of basic and applied tumor immunology in the development of cancer immunotherapies, particularly for lymphomas and melanomas. One of the largest obstacles to overcome in utilizing the body’s own immune system against tumors is the suppression of anti-tumor T-cell activity by several factors. These factors include inhibitory signals from the T-cell receptors CTLA-4 and PD1, and the overall inhibitory effects of regulatory T-cells. One method of improving the anti-tumor activity of the immune system is known as immunotransplantation, which involves the transplantation of vaccine-primed, tumor-specific T-cells into a lymphodepleted patient. A patient’s T-cells are first harvested and vaccinated against tumor antigens such as CTLA-4 and PD-1. These vaccine-primed, tumor-specific T-cells are then grown ex vivo and re-infused into the patient following immunodepletion by high-dose chemotherapy or radiation. The immunodepleting component of this procedure serves as a way of “emptying” the patient of all prior inhibitory signals, and has been shown to preferentially encourage the growth of anti-tumor T-cells versus regulatory T-cells. In essence, the idea is to reset the environmental conditions of a patient’s immune system, removing the inhibitory signals and allowing T-cells every opportunity to recognize and destroy tumor cells. Our lab has the relatively unique opportunity to perform correlative studies on primary patient tumor samples from early phase clinical trials and to continually develop advancements in those trials based on what is learned.