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

Natural cytotoxicity trigger receptor 3 ligand 1 (B7-H6) is a transmembrane protein and a member of the B7 family of immune-regulating molecules [UniProt Q68L92]. It functions as a specific ligand for the activating receptor NKp30 (NCR3) expressed on natural killer (NK) cells, playing a pivotal role in the innate immune system's ability to detect and eliminate stressed or transformed cells [PMID: 19525962]. B7-H6 is characterized by its lack of expression in healthy adult tissues and its high prevalence on the surface of various tumor types, including lymphomas, melanomas, and carcinomas of the breast and ovary [PMID: 33453157]. Upon binding to NKp30, B7-H6 triggers NK cell degranulation and the production of inflammatory cytokines, such as interferon-gamma, which directly contribute to tumor cell lysis [PMID: 21441454]. A significant challenge in targeting B7-H6 is the tumor-mediated shedding of the protein's extracellular domain, resulting in soluble B7-H6 (sB7-H6) that acts as a decoy to neutralize NK cell activity and facilitate immune escape [PMID: 25639281]. Therapeutic strategies targeting B7-H6 are currently in clinical and preclinical development, including bispecific T-cell engagers (BiTEs) like BI 765049, trispecific killer engagers (TriKEs) like GTB-5550, and chimeric antigen receptor (CAR) therapies [PMID: 30104343].

Other names

NCR3LG1B7H6B7-H6Natural cytotoxicity trigger receptor 3 ligand 1

Redirection of effector cells (T cells or NK cells) to B7-H6-expressing tumor cells, triggering targeted cytotoxicity and cytokine release.