Role of ADAM17 as a regulatory checkpoint of CD16A in NK cells and as a potential target for cancer immunotherapy.

摘要: Human NK cell antitumor activities involve Ab-dependent cell-mediated cytotoxicity (ADCC), which is a key mechanism of action for several clinically successful tumor-targeting therapeutic mAbs. cells exclusively recognize these Abs by the Fcγ receptor CD16A (FcγRIIIA), one their most potent activating receptors. Unlike other receptors on cells, undergoes rapid down-regulation in expression proteolytic process following activation with various stimuli. In this review, role disintegrin and metalloproteinase-17 (ADAM17) cleavage as regulatory checkpoint discussed. Several studies have examined effects inhibiting ADAM17 or directly during engagement Ab-coated tumor resulted strengthened Ab tethering, decreased detachment, enhanced signaling cytokine production. However, either manipulation ADCC varied between studies, may be due to dissimilar assays contribution different killing processes cells. Of importance that under circumstances, including microenvironment patients, down-regulate appears impair function. Considerable progress has been made development inhibitors, human mAbs advantages high specificity increased half-life vivo. These inhibitors provide means increasing potency and/or production an immunosuppressive microenvironment, if used combination cell-based adoptive immunotherapies improve efficacy.