Analysis of Immune Escape from Melanoma Peptide Vaccine Therapy

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MART-1 is a good candidate peptide for immunotherapy against HLA-A2 patients with melanoma, since it is a highly immunogenic antigen recognized by HLA-A2 cytotoxic T cells and expressed in the majority of melanoma lesions. In the present study, the expression of MART-1 and HLA-A2 on melanocytic cells and CD8 T cell infiltrate was analyzed. MART-1 was expressed in most of melanocytic lesions but it was down regulated in metastatic lesions, while HLA-A2 was downregulated with melanoma disease progression. CD8 T cell infiltrate was closely associated with HLA-A2 expression on melanoma cell. Expression of HLA-A2 was significantly associated with the expression of LMP and TAP molecules, which are involved in peptide presentation to CDS T. Furthermore, concomitnt down regulation of MART-1 and HLA-A2 in melanoma cells correlated with poor prognosis. In addition, IFN-gamma could induce the up regulation of HLA class I, LMP and TAP molecules in cultured melanoma cells. These data suggest that the mechanisms of immune escape from peptide therapy are as follows : 1) down regulation of peptide, 2) down regulation of HLA class I or A2, 3) down regulation of LMP or TAP molecules. MART-1 and HLA-A2 expression in melanoma lesions should be analyzed for selection of the patients eligible for MART-1 based immunotherapy and monitoring emerge of melanoma cells resistant to T cell therapy.