KLRK1 and melanoma: Soluble NKG2D ligands shedding by tumors is metalloproteinases-dependent236 and could lead to high levels of NKG2D ligands in the sera and the tumor microenvironment to the point that NKG2D ligands inhibition with antibodies could enhance CTLA-4 and PD-1 immune checkpoint blockades.237,238 Soluble sMICA and sULBP2 levels in the serum of patients with oral squamous cell carcinoma, melanoma, and NSCL correlated with disease progression.239–241