As the primary barrier between the body and the outside world the skin functions as a unique immune organ, at the intersection of adaptive and innate immune responses. The importance of skin-resident immune cells is demonstrated through several lines of evidence. First, successful vaccination strategies to cytolytic viruses rely on delivery of vaccine antigens to the skin including vaccinia and dermally-delivered influenza. Second, innate immune adjuvants that act on the cutaneous immune network (imiquimod, resiquimod) can lead to the regression of lentigo maligna and superficial spreading basal cell cancers. Third, steady state immune surveillance is critical to prevent skin cancers as evidenced by the markedly increased incidence of cutaneous neoplasias observed in renal transplant recipients maintained on immunosuppressive agents. Despite the immune-responsive nature of skin cancers and the potential for skin resident immune cells to mediate vaccine responses, vaccines have not been generated to prevent the formation of skin cancers. Improved understanding of immune surveillance in the cutaneous microenvironment is needed. A major focus of our program is to study Dendritic Cells (DC) in the cutaneous and local lymphoid environment- specialized cells which train T cells to respond to tumor and viral antigens. Our studies include identifying a role of DC in surveying skin and local lymphoid tissue as cancers arise, as well as finding ways to enhance DC function in ways that may be applied to cancer vaccines.