C-MYC-INDUCED NATURAL-KILLER-CELL SENSITIVITY OF HUMAN-MELANOMA CELLS IS REVERSED BY HLA-B27 TRANSFECTION

In human melanoma, activation of the c-myc oncogene results in locus-specific down-modulation of the HLA-B antigen expression. Moreover, overexpression of c-myc induces an increase of natural killer (NK) sensitivity of the tumor cells.To show that this effect on susceptibility to NK cells is mediated by the down-modulation of the HLA-B expression rather than by the activation of the oncogene, we supertransfected a c-myc transfectant with the gene encoding the HLA-B27 protein. The resulting supertransfectants with HLA-B27 surface expression were all less sensitive to NK cells than their parental cell line and showed a level of resistance equal to the original melanoma cell line with low c-myc expression. This indicates that the induction of NK sensitivity by c-myc activation in human melanoma cells is mediated through down-modulation of the HLA-B expression. These data also imply differential effects of HLA-A and HLA-B molecules on lysis by NK cells, because the level of NK susceptibility can apparently be defined by the level of HLA-B, irrespective of a substantial level of HLA-A expression present in the tumor cells.