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

Journal of Leukocyte Biology
Jianming WuBruce Walcheck

Abstract

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. Human NK cells exclusively recognize these Abs by the Fcγ receptor CD16A (FcγRIIIA), one of their most potent activating receptors. Unlike other activating receptors on NK cells, CD16A undergoes a rapid down-regulation in expression by a proteolytic process following NK cell activation with various stimuli. In this review, the role of a disintegrin and metalloproteinase-17 (ADAM17) in CD16A cleavage and as a regulatory checkpoint is discussed. Several studies have examined the effects of inhibiting ADAM17 or CD16A cleavage directly during NK cell engagement of Ab-coated tumor cells, which resulted in strengthened Ab tethering, decreased tumor cell detachment, and enhanced CD16A signaling and cytokine production. However, the effects of either manipulation on ADCC have varied between studies, which may be due to dissimilar assays and the contribution of different killing processes by NK cells. Of importance is that NK cells under various circumstances, including in the tumor microenvironment of patients, down-regulate CD16A and this appea...Continue Reading

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Citations

Mar 10, 2020·Journal of the Chinese Medical Association : JCMA·Wen-Ling Lee, Peng-Hui Wang
Sep 16, 2020·Journal of Leukocyte Biology·Claudia CantoniMassimo Vitale
Feb 18, 2020·Frontiers in Immunology·Gustavo Rodrigues RossiFernando Souza-Fonseca-Guimaraes
Apr 11, 2020·Cancers·Christian Sordo-BahamondeSegundo Gonzalez
Sep 13, 2019·Expert Opinion on Biological Therapy·Bruce Walcheck, Jianming Wu
Mar 11, 2020·Frontiers in Immunology·Aviad Ben-ShmuelMira Barda-Saad
Sep 3, 2019·Frontiers in Immunology·Olivier LucarStephanie Jost
Nov 5, 2019·Cancer Immunology Research·Karrune V Woan, Jeffrey S Miller
Nov 11, 2019·Molecular Therapy : the Journal of the American Society of Gene Therapy·Emily J PomeroyBranden S Moriarity
Feb 20, 2021·Critical Reviews in Oncology/hematology·Mélanie GauthierVéronique Decot
Apr 3, 2021·Frontiers in Immunology·Alexandros KarampatzakisDaniel M Davis
Jun 1, 2021·Frontiers in Oncology·Verena Waller, Martin Pruschy
Jul 31, 2021·Molecular Diagnosis & Therapy·Shee Kwan PhungMartin Felices
Aug 10, 2021·Frontiers in Immunology·Hemant K MishraBruce Walcheck
Aug 3, 2021·The Journal of Allergy and Clinical Immunology·Galam LeemEui-Cheol Shin

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