PhD

dissertationUltraviolet light (UV) irradiation can cause the development of skin tumors in experimental animals. The mechanism whereby UV irradiation is capable of inducing neoplasia is unknown. Recently, it has been reported that most UV-induced skin tumors in mice will grow progressively within the autochthonous host, but are rejected when transplanted into normal syngeneic hosts unless the latter have been immunosuppressed in some manner. However, the interesting observation has been made that following sub-carcinogenic UV exposures, normally tumor resistant mice also support the progressive growth of transplanted UV-induced tumors. These phenomena form the basis of an unusual model for study host-tumor interactions. In this system syngeneic tumors are rejected by normal hosts, and susceptibility to UV-induced tumors appears to be immunologically regulated by suppressor T lymphocytes. Ultraviolet light irradiation of mice, sufficient to induce tumor susceptibility, does not function as a nonspecific immunosuppressant. Various in vivo and in vitro assays of immune competence demonstrate that UV treated mice are immunologically similar to normal mice except for the inability to reject implanted UV-induced tumors. The UV-induced suppression of tumor responses in mice appears to be specific, cell-medicated, and transferable with lymphocytes. The cells mediating suppression can be obtained from the spleen or lymph nodes of UV treated mice, do no adhere to nylon wool columns, and appear to be T lymphocytes. The suppressor cells are capable of maintaining suppressive activity for several weeks when transferred into normal mice. In adoptive transfer assays, UV-induced suppressor cells prevent the development and expression of primary anti-UV tumor responses as well as to suppress the expression of pre-established tumor immunity. Evidence is presented which suggests that adoptively transferred suppression inhibits specific components of the anti-tumor response, Ultraviolet light-induced tumors are though to possess unique and common antigens and the suppressor T cells inhibit effector responses directed against the common tumor antigens. This dissertation begins with a review of work by me and other investigators on the transplantation characteristics of UV-induced tumors in syngeneic mice. There follow four publications which pertain to how UV irradiation suppresses the immune response of normal mice to transplanted UV-induced tumors. Lastly, a discussion of alternative hypotheses is presented to account for the effect of UV irradiation on the anti-tumor response in mice