Moreover, our studies have provided evidence that, under conditions of chronic CD16 engagement, the activation of SHP-1 tyrosine phosphatase induces a wide-range functional exhaustion status, which hampers NK cell killing triggered by either CD16 or other activating receptors, such as NKG2D and NKp46 [111]; along this line, ex vivo analysis of rituximab-treated DLBCL patients revealed a marked and prolonged therapy-induced reduction of both “natural” and CD16-dependent NK cytotoxic activities, accompanied by the downmodulation of CD16 and NKG2D-activating receptors [112]. This evidence concerns the gene FCGR3A and diffuse large B-cell lymphoma.