CD48-expressing non-small-cell lung cancer cells are susceptible to natural killer cell–mediated cytotoxicity

The susceptibility of cancer cells to natural killer (NK) cell-mediated cytotoxicity depends on the balance of activating and inhibitory ligands expressed on their surface. Although many types of cancer cells are killed by NK cells, non-small-cell lung cancer (NSCLC) cells are relatively resistant to NK cell-mediated cytotoxicity. In this study, we showed that several NSCLC cell lines have differential sensitivity to NK cell-mediated cytotoxicity: NCI-H522 cells were highly sensitive, but A549, NCI-H23, NCI-H1915, and NCI-H1299 were resistant. Among activating ligands such as CD48, HLA-A/B/G, ICAM-1, MICA/B, and ULBPs, only CD48 rendered NCI-H522 cells susceptible to NK cell-mediated cytotoxicity, which was proved by using CD48 siRNA and neutralizing antibody. CD48-positive NCI-H522 cells established a more stable contact with NK cells than did CD48-negative A549 and CD48 siRNA cell-transfected NCI-H522 cells. Taken together, these data demonstrate that CD48-positive NSCLC cells might be susceptible to NK cell-mediated cytotoxicity, which provide information on how to stratify NSCLC patients potentially responsive to NK-cell therapy.