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

Natural cytotoxicity receptor 3 ligand 1 (B7-H6) is a type I transmembrane protein belonging to the B7 family of immune-regulating ligands (UniProt Q682Q4). It is characterized by its restricted expression pattern, being largely absent from healthy tissues but frequently upregulated on the surface of various tumor cells, including those in breast cancer, melanoma, and various hematologic malignancies (PubMed: 19525962). B7-H6 serves as a potent activator of the innate immune system by binding to the NKp30 receptor on Natural Killer (NK) cells, which induces cytokine production and cytolytic activity against the expressing cells (PubMed: 21441448). Due to its tumor-specific expression, B7-H6 is an attractive target for cancer immunotherapy, with several strategies under investigation, including bispecific antibodies like BI 765049 and B7-H6-targeted CAR-T cells (NCT04430829). A notable challenge in targeting B7-H6 is its susceptibility to proteolytic shedding by metalloproteinases, which releases a soluble form (sB7-H6) that can act as a decoy, potentially neutralizing therapeutic agents and inhibiting NK cell activation (PubMed: 22566019).

Other names

B7 homolog 6B7-H6NCR3LG1B7H6DKFZp686O24166

B7-H6 acts as a ligand for the NKp30 activating receptor on NK cells. Therapeutic strategies include bispecific T-cell engagers (BiTEs) that bridge B7-H6 on tumor cells with CD3 on T-cells, and CAR-T cells engineered to recognize B7-H6, both leading to targeted tumor cell lysis.