Natural killer cell p30-related protein ligands (NKp30 ligands)

Natural killer cell p30-related protein (NKp30) ligands, primarily B7-H6 and BAG6 (also known as BAT3), are critical mediators of the innate immune response against transformed and infected cells. B7-H6 is a member of the B7 family that is selectively expressed on the surface of various tumor cells, including lymphomas, melanomas, and carcinomas, while remaining largely absent from healthy tissues (Brandt et al., 2009). BAG6 is a multifunctional protein that can be expressed on the surface of dendritic cells (DCs) to facilitate NK-DC crosstalk or released by tumor cells to modulate NK cell activity (Pogge von Strandmann et al., 2007). These ligands bind to the NKp30 receptor on NK cells, triggering the release of cytotoxic granules and interferon-gamma to eliminate target cells. In clinical development, these ligands are targeted by chimeric antigen receptor (CAR) T and NK cells, as well as bispecific engagers designed to bridge NK cells to tumor-associated B7-H6. A major challenge in targeting these ligands is the proteolytic shedding of B7-H6 from the cell surface, which produces soluble forms that act as decoys and inhibit NK cell activity (Schlecker et al., 2010).

Other names

B7-H6NCR3LG1BAG6BAT3HLA-B-associated transcript 3B7 homolog 6NCR3 ligands

Binding to the NKp30 (NCR3) receptor on Natural Killer cells to induce activating signals, leading to the release of cytotoxic granules (perforin/granzyme) and pro-inflammatory cytokines (IFN-gamma) against target cells.