RT Journal Article ID 439c539443e54a8b A1 Zingoni, Alessandra A1 Vulpis, Elisabetta A1 Nardone, Ilaria A1 Soriani, Alessandra A1 Fionda, Cinzia A1 Cippitelli, Marco A1 Santoni, Angela T1 Targeting NKG2D and NKp30 Ligands Shedding to Improve NK Cell−Based Immunotherapy JF Critical Reviews™ in Immunology JO CRI YR 2016 FD 2017-05-31 VO 36 IS 6 SP 445 OP 460 K1 NK cells K1 immunotherapy K1 NKG2D K1 NKp30 K1 shedding AB Natural killer (NK) cells are critical immune effector cells capable of mediating antitumor responses. These cytotoxic lymphocytes recognize transformed cells through a mechanism mainly dependent on the engagement of several activating receptors. However, many tumors have developed strategies to evade immunosurveillance and detection by NK cells. A relevant immune escape mechanism is the down regulation of NK cell activating ligands on the surface of tumor cells by proteolytic shedding mediated by different members of metalloproteinase families. Here, we consider two important NK activating receptors, namely NKG2D and NKp30, the ligands (i.e., MICA/B, ULBPs, and B7-H6) of which can be released by cancer cells through proteolytic cleavage. Modulation of ligand shedding in response to cancer therapy is also examined, and we discuss how metalloproteinases implicated in the ligand cleavage could be targeted in novel therapeutic schemes to counteract tumor escape from stress-elicited immune responses. PB Begell House LK https://www.dl.begellhouse.com/journals/2ff21abf44b19838,556ac5b96519764b,439c539443e54a8b.html