Natural cytotoxicity triggering receptor 3 ligands (NKp30 ligands) (NKp30L)

NKp30 ligands are a group of molecules expressed on the surface of tumor cells or virally infected cells that interact with the activating receptor NKp30 (NCR3) on Natural Killer (NK) cells (Brandt et al., 2009, J Exp Med). The most prominent ligand is B7-H6 (NCR3LG1), a member of the B7 family that is specifically upregulated in various cancers—such as melanoma, lymphoma, and carcinomas—while remaining absent from most healthy tissues (Kruse et al., 2023, Front Immunol). Other ligands include BAG6 (also known as BAT3), which can be presented on the cell surface or released via exosomes to trigger NK cell activity, and Galectin-3, which may act as an inhibitory ligand (Pogge von Strandmann et al., 2007, J Exp Med). Viral proteins, such as the Human Cytomegalovirus (HCMV) protein pp65, also bind NKp30, often serving as a mechanism for viral immune evasion (Arnon et al., 2005, Nat Immunol). Therapeutic strategies targeting these ligands include B7-H6-specific CAR-T cells, bispecific antibodies (e.g., B7-H6/CD3), and NKp30-Fc fusion proteins designed to enhance NK cell-mediated anti-tumor immunity. However, the shedding of soluble ligands like sB7-H6 can act as a decoy, neutralizing these therapies and posing a challenge for clinical efficacy.

Other names

B7-H6NCR3LG1BAG6BAT3Galectin-3NCR3 ligandsNKp30-L

Activation of NK cell-mediated cytotoxicity through binding and signaling via the NKp30 (NCR3) receptor.