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. This evidence concerns the gene KLRK1 and neoplasm.