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 downmodulation 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.