Prolonged upregulation of the expression of HLA class I antigens and costimulatory molecules on melanoma cells treated with 5-aza-2 '-deoxycytidine (5-AZA-CdR)

The immunogenic potential of melanoma cells and their recognition by the ho st's cytotoxic cells depends on the presence and on the level of expression of human leukocyte antigen (NLA) class I antigens, costimulatory molecules and melanoma-associated antigens (MAA), on neoplastic cells. In this study , we demonstrate that the DNA hypomethylating agent 5-aza-2'-deoxycytidine (5-AZA-CdR), Significantly (p < 0.05) enhanced the constitutive expression of HLA class I antigens, HLA-A1 and -A2 alleles, and of the costimulatory m olecules intercellular adhesion molecule-1 and lymphocyte function-associat ed antigen-3, on a panel of 12 melanoma cells. This upregulation peaked at day 4, slowly decreased thereafter, and returned to baseline levels 32 days after the end of treatment. In addition, treatment with 5-AZA-CdR induced a persistent expression of MAGE-1 in Mel 275 melanoma cells; this was still detectable, by reverse transcriptase polymerase chain reaction, 60 days af ter the end of treatment. In contrast, 5-AZA-CdR did not affect the constit utive expression of the high molecular weight-MAA by the melanoma cells inv estigated. These observations, together with data obtained comparing the ef fect of 5-AZA-CdR with that of interferon-gamma, strongly suggest that 5-AZ A-CdR may have prospective therapeutic implications in active and/or passiv e specific immunotherapy for human melanoma.