Natural cytotoxicity receptor ligands (NCR ligands) (NCR ligands)

Natural cytotoxicity receptor (NCR) ligands are a diverse group of molecules expressed on the surface of tumor cells or virus-infected cells that serve as stress signals to the immune system (Kruse et al., 2014). These ligands are recognized by the activating receptors NKp46, NKp44, and NKp30, which are primarily expressed on Natural Killer (NK) cells (Pazina et al., 2017). Upon binding, these receptors trigger NK cell activation, leading to the release of cytotoxic granules and the secretion of pro-inflammatory cytokines like IFN-gamma. In oncology, many tumor cells upregulate specific NCR ligands, such as B7-H6 (a ligand for NKp30), to signal their transformed state (Brandt et al., 2009). However, tumors often employ escape mechanisms, such as shedding these ligands into the microenvironment to act as decoys or downregulating their expression to avoid detection (Schlecker et al., 2014). Therapeutic strategies currently under investigation include the development of bispecific NK cell engagers and CAR-NK cells designed to specifically target these ligands to enhance anti-tumor immunity (Barrow et al., 2018).

Other names

Tumor cell ligands of natural cytotoxicity receptorsNKp30 ligandsNKp44 ligandsNKp46 ligandsB7-H6NCR3LG1BAG6BAT3PDGF-DD

Binding to activating natural cytotoxicity receptors (NKp30, NKp44, NKp46) on NK cells to trigger degranulation and cytokine release against tumor cells.