Tumor Escape from Immune Recognition Lethal Recurrent Melanoma in a Patient Associated with Downregulation of the Peptide Transporter Protein TAP-1 and Loss of Expression of the Immunodominant MART-1/Melan-A Antigen

In the last few years, mutiple protein target antigens for im-munorecognition by T cells have been identified on human melanoma. How melanoma lesions escape from functional antigen-specific immune recognition remains poorly under-stood. We have identified the concomitant loss of the immu-nodominant T cell–defined MART-1/Melan-A antigen and downregulation of the TAP-1 gene in a recurrent metastatic melanoma that was resected in 1993. This phenotype was not observed for an earlier autologous melanoma lesion re-sected in 1987. The “antigen loss ” could be restored in the variant tumor cell line by simultaneously providing both the MART-1/Melan-A gene (by retroviral transfer) and the TAP-1 gene (by a bioballistic approach) resulting in tumor cell sensitivity to MART-1/Melan-A–specific cytotoxic T lymphocytes. This suggests that tumor escape from immune surveillance may have occured in vivo as a sequential result of