The susceptibility to natural killer cell-mediated lysis of HLA class I-positive melanomas reflects the expression of insufficient amounts of different HLA class I alleles

Daniela Pende, Laura Accame, Laura Pareti, Arabella Mazzocchi, Alessandro Moretta, Giorgio Parmiani, Lorenzo Moretta

Research output: Contribution to journalArticle

Abstract

NK cells selectively lyse tumor cells which do not express one or more MHC class I alleles. The ability to discriminate between self normal or tumor cells is due to the expression of MHC class I-specific killer inhibitory receptors (KIR). In the present study we analyzed melanoma cell lines which were highly susceptible to NK cell-mediated lysis in spite of the expression of a complete set of HLA class I alleles. Quantitative analysis of the HLA class I expression using allele-specific monoclonal antibodies (mAb) revealed a down-regulation of all HLA class I molecules. Treatment of melanoma cells with IFN-γ resulted in up-regulation of all HLA class I alleles that was paralleled by the acquisition of resistance to lysis. That resistance to lysis reflected the up-regulation of HLA class I molecules was revealed by the finding that mAb-mediated masking of either KIR or their HLA class I ligands completely restored the melanoma cell lysis. These results were obtained by the use of selected NK cell clones derived either from allogeneic or autologous donors. In addition, similar results were obtained using in vitro expanded autologous NK cell populations. Our data indicate that NK cells can lyse not only melanoma cells which have lost the expression of one or more HLA class I alleles but also cells expressing a decreased amount of class I molecules.

Original languageEnglish
Pages (from-to)2384-2394
Number of pages11
JournalEuropean Journal of Immunology
Volume28
Issue number8
DOIs
Publication statusPublished - Aug 1998

Keywords

  • HLA class I
  • Killer inhibitory receptor
  • Melanoma cell
  • NK cell

ASJC Scopus subject areas

  • Immunology

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