In addition, since PMA may induce the increased transcription of ADAM17 through NFkB and ERK1/2 signaling (46), which can be activated by IL-15 (47), we speculate that, in metastatic melanomas, the cleaved biological active complex increasing the enzymatic activity of ADAM17, and its transcription creates a self-perpetuating deleterious loop, leading to the decreased proliferation of infiltrating NK cells (32). This evidence concerns the gene NFKB1 and melanoma.