Heterogeneity in expression of human leukocyte antigens and melanoma-associated antigens in advanced melanoma

Abstract

The study of tumor immunology has led to many innovative therapeutic strategies for the treatment of melanoma. The strategies are primarily dependent on melanoma-associated antigen peptide vaccination or T-cell-based therapy. These immunotherapies are totally reliant on proper copresentation of human leukocyte antigen class I molecules in sufficient quantity and the presence and availability of melanoma-associated antigenic peptides. Altered expression of either HLA class I molecules or melanoma antigens is known to occur. These defects lead to altered manufacture and copresentation of HLA class I molecules with melanoma-associated antigens to T-cells. Defects in any one combination can lead to loss of recognition of melanoma cells and their subsequent destruction by cytotoxic T-lymphocytes. Thus, these immunotherapy strategies can be thwarted by defects or heterogeneity of expression of human leukocyte antigen class I or of melanoma-associated antigens.