Unbalanced expression of HLA-A and -B antigens: A specific feature of cutaneous melanoma and other non-hemopoietic malignancies reverted by IFN-gamma

Conflicting evidences suggested that levels of HLA-A and -B antigens expres sed on normal and neoplastic cells of given individuals are genetically pre determined, or, on the other hand, regulated by molecular mechanisms genera ting the down regulated expression of HLA-B antigens frequently observed on melanoma cells. In our study, we quantitated, both at the protein and mRNA level, the amounts of HLA-A and -B antigens constitutively expressed on 23 primary cultures of metastatic melanomas and on autologous peripheral bloo d mononuclear cells (PBMC). Flow cytometric analyses identified a significa ntly (p < 0.01) lower expression of HLA-B antigens on melanoma cell culture s but not on autologous PBMC. Consistently, lower amounts of HLA-B antigens mRNA were detected by RNase protection assay exclusively in neoplastic cel ls. This unbalanced expression of HLA-A and -B antigens was readily reverte d by interferon (IFN)-<gamma> but not by the DNA hypomethylating agent 5-az a-2'-deoxycytidine in 4 melanoma cell cultures investigated. Significantly (p < 0.05) lower levels of HLA-B antigens were also detected on cells from solid malignancies of different histotypes but not on neoplastic cells from hemopoietic neoplasms; levels of HLA-B antigens were rapidly up-regulated by IFN-<gamma> exclusively on non-hemopoietic transformed cells. Together, these data strongly argue against a genetic predetermination of the amounts of HLA-A and -B antigens expressed on normal and neoplastic cells of disti nct melanoma patients and suggest that constitutively low levels of HLA-B a ntigens are a specific feature of non-hemopoietic transformed cells that is controlled by common regulatory mechanism(s) and that is possibly shared b y non-hemopoietic normal cells. (C) 2001 Wiley-Liss.