In line with the decrease in immune cell activity due to soluble NKG2D ligands, checkpoint inhibition therapy using PD-1 antibodies in melanoma was found to be most effective in absence of shed ligands (66), supporting the view that NKG2D ligands need to be taken in consideration for therapies that are not “intentionally” involve the NKG2D-axis. This evidence concerns the gene KLRK1 and melanoma.