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

Aldo Gasparollo, Sandra Coral, Marina Ciullo, Antonella Prisco, Ilaria Cattarossi, Luca Sigalotti, Maresa Altomonte, John Guardiola, Michele Maio

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)500-507
Number of pages8
JournalInternational Journal of Cancer
Volume91
Issue number4
DOIs
Publication statusPublished - Feb 15 2001

Keywords

  • Hemopoietic tumors
  • HLA class I antigens
  • IFN-γ
  • Melanoma
  • Solid tumors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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