B7 homolog 6 (B7-H6) (B7-H6)

B7 homolog 6 (B7-H6), encoded by the NCR3LG1 gene, is a member of the B7 family of immune-regulating proteins and serves as the primary ligand for the activating receptor NKp30 (NCR3) found on Natural Killer (NK) cells (Brandt et al., 2009, J. Exp. Med.). While B7-H6 is generally absent from healthy tissues, it is frequently overexpressed on the surface of various malignant cells, including multiple myeloma plasma cells, where it facilitates immune recognition (Fionda et al., 2017, Leukemia). The interaction between B7-H6 and NKp30 triggers NK cell degranulation and the release of pro-inflammatory cytokines, leading to the direct lysis of the tumor cell. However, myeloma cells often employ immune evasion strategies by shedding B7-H6 from the cell surface via metalloproteinases, resulting in soluble B7-H6 (sB7-H6) that acts as a decoy to inhibit NK cell function (Schlecker et al., 2010, Cancer Res.). Due to its tumor-restricted expression profile, B7-H6 is a prominent therapeutic target for the development of chimeric antigen receptor (CAR) therapies and bispecific antibodies designed to bridge effector immune cells with myeloma cells (Pesce et al., 2017, Front. Immunol.).

Other names

NCR3LG1Natural cytotoxicity triggering receptor 3 ligand 1B7H6NKp30 ligand

Binding to the NKp30 receptor to trigger Natural Killer (NK) cell activation and tumor cell lysis, or serving as a tumor-associated antigen for engineered T-cell or NK-cell redirection.