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

Natural cytotoxicity triggering receptor 3 ligands (NKp30L) are a group of proteins expressed on the surface of tumor cells or virus-infected cells that serve as ligands for the activating receptor NKp30 (NCR3) found on Natural Killer (NK) cells (Brandt et al., 2009, J Exp Med). The most prominent and clinically relevant ligand is B7-H6 (NCR3LG1), a member of the B7 family that is specifically upregulated in various cancers, including lymphomas, melanomas, and carcinomas, while remaining largely absent from healthy tissues. Other identified ligands include BAG6 (also known as BAT3), which can be expressed on the cell surface or released via exosomes, and Galectin-3 (Pogge von Strandmann et al., 2007, Immunity). Binding of these ligands to NKp30 triggers NK cell activation, leading to the secretion of proinflammatory cytokines like IFN-gamma and the release of cytotoxic granules to eliminate the target cell. However, many tumors employ immune evasion strategies such as the proteolytic shedding of B7-H6, resulting in soluble decoys that block NKp30 and impair NK cell function (Schlecker et al., 2014, Cancer Res). Therapeutic approaches currently under investigation include B7-H6-targeted CAR-T cells and bispecific antibodies designed to redirect effector cells to tumor sites and overcome immune suppression.

Other names

B7-H6NCR3LG1B7 homolog 6BAG6BAT3HLA-B-associated transcript 3Galectin-3HCMV pp65

Activation of NK cells through NKp30 binding or redirection of T-cells/NK cells to ligand-expressing tumor cells.