It has long been known that, in addition to being carcinogenic via DNA damage and mutations, solar UV radiation induces local and systemic immune suppression which represents a major risk for skin cancer induction and progression in sun-exposed areas. The process is mostly related to direct LC damage through induction of apoptosis and impairment of antigen-presenting function. Moreover, UV radiation elicits an inflammatory response and subsequent recruitment of immune cells, including CD36+ monocytic cells. These cells colonize the epidermis in the days following UV exposure and are the major source of immunosuppressive cytokines such as IL-10. All these mechanisms ultimately lead to impaired cell-mediated reactions and establishment of immune tolerance.