Hypoxia, low glucose concentration, cytokines, tumor-derived metabolites, such as adenosine and lactate, tumor cell-derived factors such as IL-6, IL-10, TGF-β, IDO, prostaglandin E2 (PGE2), and vascular endothelial growth factor (VEGF) (105, 106), including co-inhibitory molecules in the TME such as tryptophan catabolites, dickkopf-related protein 2 (DKK2), soluble HLA-G, soluble NKG2D ligands, and galactin-3 (soluble inhibitory receptor for NKp30) inhibit NK cell activity (107). Here, DKK2 is linked to neoplasm.