UV-INDUCED N-RAS MUTATIONS ARE T-CELL TARGETS IN HUMAN-MELANOMA

Human cutaneous melanoma is heterogeneous with respect to the genetic aberrations involved and the genes altered are potential targets for t he immune system. The incidence of cutaneous melanoma is known to be l inked to UV peak exposure, and the N-ras oncogene is dearly one of the genes involved in the UV carcinogenesis in melanoma. It is mutated in a significant proportion of melanomas and therefore may serve as a ta rget forT cells. Here, we report that an human leukocyte antigen-A2 bi nding peptide CLLDILDTAGL, encompassing the frequently found 61-Leu mu tation in N-ras, induces cytotoxic T lymphocytes from healthy donor bl ood that lyse 61-Leu N-ras-transfected melanoma cells. Furthermore, we have found an association between the presence of N-ras mutations and clinical response to immunotherapy with interleukin-2 plus interferon in a group of stage IV melanoma patients. Although the overall surviv al of these patients was not affected by the N-ras status of their mel anomas, these studies suggest that mutated N-ras may provide a target for cytotoxicT lymphocytes in melanoma patients.