Collectively, all our data strongly argue against an NKG2D down-regulation by shed sMICA, while some previous observations on NKG2D down-regulation in cancer patients may be attributable to MICA embedded in exosomes or other tumor-derived vesicles or by other tumor-derived soluble factors such as TGF-β (20, 45, 46). Here, KLRK1 is linked to cancer.