sMIC are highly immune suppressive by multiple mechanisms, such as disturbing NK cell homeostatic maintenance and function [16, 20, 21], facilitating expansion of myeloid derived suppressor cells (MDSC) in tumor microenvironment [22], and more profoundly, impairing antigen-specific CD8 T cell activation via down-regulating NKG2D co-stimulation and destabilizing the TCR/CD3 signaling molecule CD3ζ through activation of caspase 8 pathway [20, 23]. This evidence concerns the gene KLRK1 and neoplasm.