HPSE and neoplasm: It is an attractive hypothesis to speculate that NK cells could utilize the NCRs to sense changes in HSPGs in the tumor microenvironment or possibly even during infection to activate NK cell cytotoxicity and IFN-γ secretion, particularly since several cancers exhibit aberrant regulation of key HS biosynthetic enzymes, such as 3-O- and 6-O-Sulfotransferases, and catabolic enzymes, such as heparanase and the HS endosulfatases, SULF1 and SULF2 (105).