Natural cytotoxicity trigger receptor 3 (NCR3) (NKp30)

Natural cytotoxicity trigger receptor 3 (NCR3), widely known as NKp30, is a type I transmembrane glycoprotein and a member of the natural cytotoxicity receptor (NCR) family [1, 4]. It is constitutively expressed on mature Natural Killer (NK) cells and plays a pivotal role in the innate immune response by triggering NK cell activation and cytotoxicity upon binding to specific ligands [3, 4]. Key ligands include B7-H6, which is often overexpressed on the surface of various tumor cells, and BAG6 (BAT3), a nuclear protein released by stressed or infected cells [3]. In the context of oncology, NKp30 is a significant therapeutic target; its activation can enhance the anti-tumor activity of NK cells, while its downregulation or the presence of soluble decoy ligands (like sNKp30 or sB7-H6) is associated with tumor immune evasion and poor prognosis [3, 4]. Therapeutic strategies include the development of monoclonal antibodies, bispecific NK cell engagers (BiKEs), and CAR-NK cells designed to leverage the NKp30 signaling pathway to eliminate malignant cells [3, 5]. Sources: [1] UniProt (O14931); [2] NCBI Gene (259197); [3] Kruse et al., J Hematol Oncol (2023); [4] Barrow et al., Front Immunol (2019); [5] Zhang et al., Front Immunol (2021).

Other names

CD337NCR3Natural killer cell p30-related protein1C7LY117

Agonistic activation of NK cell-mediated cytotoxicity and cytokine production through ITAM-containing adapter proteins (CD3-zeta or FcεRIγ) upon binding to ligands such as B7-H6 or BAG6.