Natural cytotoxicity triggering receptor 3 ligand (NKp30L) (NKp30L)

Natural cytotoxicity triggering receptor 3 (NCR3, also known as NKp30) ligands are a group of molecules expressed on the surface of tumor or stressed cells that serve as critical recognition signals for the innate immune system. The primary protein ligand, B7-H6 (NCR3LG1), is a member of the B7 family and is characteristically expressed on various human cancer cells but is largely absent from healthy tissues [Brandt et al., 2009]. Other ligands include BAG6 (BAT3), a chaperone protein that can be presented on the cell surface or released via exosomes to activate NK cells, and specific heparan sulfate proteoglycans that modulate receptor-ligand interactions [Pogge von Strandmann et al., 2007; Hecht et al., 2009]. These ligands play a pivotal role in tumor immunosurveillance by binding to the NKp30 receptor, thereby inducing NK cell-mediated lysis and the secretion of pro-inflammatory cytokines like IFN-gamma. In clinical oncology, B7-H6 is being actively explored as a therapeutic target for CAR-T cell therapy and bispecific antibodies, such as BI 765049 [Schlecker et al., 2014]. However, the shedding of soluble B7-H6 by metalloproteases represents a significant mechanism of immune escape and a challenge for treatment efficacy by acting as a decoy for the NKp30 receptor.

Other names

NCR3 ligandNKp30 ligandB7-H6NCR3LG1BAG6BAT3Heparan sulfate proteoglycans

Binding to the NKp30 receptor on natural killer (NK) cells to trigger cytotoxicity and cytokine production against tumor or stressed cells.