Cross-Reactive Tumor Antigens in the Skin of Mice Exposed to Subcarcinogenic Doses of Ultraviolet Radiation

Abstract

This study suggests that cross-reactive tumor-associated antigens (TAA) are induced in the epidermis of mice exposed to subcarcinogenic doses of ultraviolet radiation (UVR). Foot-pad immunization of C3H mice with viable epidermal cells from syngeneic UVR-exposed mice induced cytotoxic cells in the draining lymph nodes (DLN). These cells were capable of lysing a battery of UVR-induced tumor targets in a short-term chromium release assay. In contrast, the DLN cells of mice immunized with epidermal cells from normal non-UVR-exposed mice did not mature into effector cells with antitumor activity. The spectrum of tumor recognition of cytotoxic cells induced by immunization with UVR-exposed epidermal cells was identical to that of cytotoxic T cells obtained from animals that were foot-pad immunized with UVR-induced tumor cells. Both cytotoxic cell populations were shown to lyse tumors of diverse origin, including syngeneic UVR- and methylcholanthrene-induced tumors, as well as allogeneic UVR-induced tumors. These cells displayed minimal lytic activity against YAC-1 lymphoma cells, peritoneal exudate cells, and concanavalin A-stimulated splenocytes. The results from this study demonstrate that antigens are expressed on UVR-exposed mouse epidermal cells prior to the emergence of skin tumors, and these antigens can induce cytotoxic cells with specificity for TAA. We conclude that the early antigenic changes observed in UVR-exposed epidermis and their effect on the host's immune system may influence the emergence and progression of UVR-induced skin cancers.