Short term exposure of the skin to ultraviolet light (UV) results in the functional deletion of particular cell types, reversible suppression of cellular and humoral immune responses to topically applied sensitizers, and expression of new antigens in the epidermis. Repeated exposures elicit specific T suppressor cells new antigens in the epidermis. Repeated exposures elicit specific T suppressor cells which inhibit anti-UV tumor responses in murine hosts. It is not known if the initial effects of UV irradiation on the skin are linked with the acquisition of the tumor susceptible state. Thus, the research program will focus on determining if early and late UV effects are related. Several parallel approaches will be applied to the problem. In addition to our present monoclonal antibodies, new ones will be made against UV-induced tumors. A battery of such reagents will be used to determine the antigenic relationships between normal skin, UV-irradiated skin, and UV-induced skin tumors. Secondly, phenotypically defined UV tumors will be used as models to represent. or to predict and retrieve normal (perhaps unrecognized) epidermal cell counterparts for studies on immunologic functions. The rationale is that detection of antigens common to UV-irradiated skin and UV-induced tumors, and skin cells with particular immunologic properties, may allow us to determine why tumor specific suppression precedes a neoplasm. Approaches for determining the biological relevance of common antigtens detected on irradiated skin and tumors include using the monclonal antibodies in vivo as idiotypic factors. It may be possible to interrupt suppressor cell networks and prevent UV-induced suppression of anti-tumo responses from occurring. Such a system may provide a model for investigating in man immunotherapy protocols aimed at deletion of suppression to common tumor antigens, thus enabling effector responses to be dominant.
