Premium
Unbalanced expression of HLA‐A and ‐B antigens: A specific feature of cutaneous melanoma and other non‐hemopoietic malignancies reverted by IFN‐γ
Author(s) -
Gasparollo Aldo,
Coral Sandra,
Ciullo Marina,
Prisco Antonella,
Cattarossi Ilaria,
Sigalotti Luca,
Altomonte Maresa,
Guardiola John,
Maio Michele
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(200002)9999:9999<::aid-ijc1076>3.0.co;2-i
Subject(s) - antigen , biology , human leukocyte antigen , pan t antigens , haematopoiesis , immunology , peripheral blood mononuclear cell , melanoma , hla b antigens , cancer research , microbiology and biotechnology , stem cell , antibody , genetics , in vitro , monoclonal antibody
Conflicting evidences suggested that levels of HLA‐A and ‐B antigens expressed on normal and neoplastic cells of given individuals are genetically predetermined, or, on the other hand, regulated by molecular mechanisms generating 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 blood mononuclear cells (PBMC). Flow cytometric analyses identified a significantly ( p < 0.01) lower expression of HLA‐B antigens on melanoma cell cultures but not on autologous PBMC. Consistently, lower amounts of HLA‐B antigens mRNA were detected by RNase protection assay exclusively in neoplastic cells. This unbalanced expression of HLA‐A and ‐B antigens was readily reverted by interferon (IFN)‐γ but not by the DNA hypomethylating agent 5‐aza‐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‐γ 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 distinct melanoma patients and suggest that constitutively low levels of HLA‐B antigens are a specific feature of non‐hemopoietic transformed cells that is controlled by common regulatory mechanism(s) and that is possibly shared by non‐hemopoietic normal cells. © 2001 Wiley‐Liss, Inc.