Top left, in red: NK cells recognize tumor targets that lack MHC, as this prevents the inhibitory response mediated by KIR. Several tumors down-regulate MHC in response to T cell immune pressure. The same pathway does not become activated in the setting of allogeneic NK cells and is only engaged when NK cell effectors recognize self MHC. Bottom, in blue: NK cell activating receptor ligands are expressed by numerous malignancies [45-60,62,242-247], and these tumors engage NK-activating receptors, some of which associate with ITAM-containing DAP10 and DAP12 to mediate NK cell activation via proteins such as Vav1 and PLCγ2. Top right, in green: NK cells are the principal effectors of ADCC, mediating tumor lysis in settings when antibodies targeting overexpressed surface targets are used. Various antibodies have been developed to recruit ADCC against tumor cells bearing targets such as Her2, CD20, EGFR, and/or CD52. These antibodies bind to the CD16 receptor, which, in turn, is associated with ITAM-containing proteins such as the TCRζ chain–leading to NK cell activation.