These phenotypes in NK cells are induced by high expression of checkpoint ligands on tumors (such as Programmed death-ligand 1 (PD-L1) and HLA-E) (69, 70), inhibitory cytokines and inhibitory soluble factors (such as TGF-β and IL-10) (71–73), hypoxia (74, 75), exposure to tumor suppressor cells (i.e., Tregs, tumor associated macrophages, and MDSCs) (76–78), and sustained chronic activation (such as sustained activation through the activating NKG2D receptor) (79, 80). The gene discussed is HLA-E; the disease is neoplasm.