Natural cytotoxicity triggering receptor 3 ligand 1 (B7-H6) (B7-H6)

Natural cytotoxicity triggering receptor 3 ligand 1 (B7-H6) is the primary ligand for the NKp30 activating receptor found on Natural Killer (NK) cells. While B7-H6 is not typically expressed on healthy tissues, it is highly upregulated on the surface of various tumor cells, including melanoma, lymphoma, and several carcinomas (Brandt et al., 2009, J Exp Med). Other ligands such as BAG6 (BAT3) and Galectin-3 also interact with NKp30, though B7-H6 remains the most prominent target for therapeutic intervention (Pogge von Strandmann et al., 2007, Immunity; Wang et al., 2011, J Biol Chem). The binding of B7-H6 to NKp30 triggers NK cell degranulation and the release of pro-inflammatory cytokines like IFN-gamma, facilitating the elimination of malignant cells. In clinical development, B7-H6 is targeted by chimeric antigen receptor (CAR) T-cells and bispecific antibodies to redirect immune effector cells to the tumor (Wu et al., 2015, Protein Cell). A significant challenge in targeting this pathway is the proteolytic shedding of B7-H6 from the tumor surface, which generates a soluble form (sB7-H6) that can inhibit NK cell function by blocking the NKp30 receptor (Schlecker et al., 2014, Cancer Res).

Other names

NCR3LG1B7H6B7-H6NKp30 ligandB7 homolog 6

Directing immune effector cells (NK or T cells) to tumor cells by binding to surface-expressed B7-H6, thereby inducing targeted tumor cell lysis and cytokine release.