A major goal of my research is to investigate approaches that overcome melanoma-mediated T cell suppression. Much of my research on the anti-melanoma activity of combined lymphopenia and immunotherapy. Based on the hypothesis that regression of established melanoma will require multiple immunotherapeutic approaches for the induction of effective anti-tumor T-cell activity, my scientific research aims to implement therapies for the induction of potent anti-tumor T-cell responses against melanoma. We aim to achieve this by: 1. Investigating experimentally the mechanisms of immune regulation induced after lymphopenia; 2. Examining the efficacy of DC-based vaccination in the setting of lymphopenia by transfer of T cells enriched in CD8+ memory T cells; and 3. Determining the efficacy of dendritic cell vaccination and CpG adjuvant therapy in combination with irradiation and adoptive T-cell transfer in a murine melanoma model. We have outlined experimental studies that are designed to continue successful preclinical efforts to generate immunization strategies against melanoma. These findings could be translated to human clinical immunotherapeutic trials. We are also is investigating the effectiveness of radiation therapy followed by T-cell transfer and dendritic cell immunotherapy for treatment of established melanoma with the goal of defining the potential of combining radiation or chemotherapy and immunotherapy for treatment of melanoma.