Natural killer cell cytotoxicity receptor 3 (NKp30) (NKp30)

Natural killer cell cytotoxicity receptor 3 (NKp30) is a type I transmembrane glycoprotein and a member of the natural cytotoxicity receptor (NCR) family, primarily expressed on mature Natural Killer (NK) cells [UniProt P14770]. Encoded by the NCR3 gene, it functions as a potent activating receptor that triggers the lysis of tumor cells and virally infected cells. The receptor recognizes specific ligands, most notably B7-H6, which is frequently overexpressed on various cancer types—including lymphoma, leukemia, and several solid tumors—but is generally absent on healthy tissues [Brandt et al., 2009; PubMed 19528259]. In the context of haNK cells (high-affinity NK cells), which are engineered NK-92 cells, NKp30-mediated signaling is a critical component of the cell's anti-tumor machinery alongside engineered CD16 [ImmunityBio, 2024]. Binding of NKp30 to its ligands leads to the phosphorylation of ITAM-containing adapter proteins, initiating a signaling cascade that results in the degranulation of cytotoxic molecules like perforin and granzymes. This pathway is a major focus for developing adoptive cell therapies and bispecific engagers aimed at treating malignancies that evade traditional immunosurveillance [Kruse et al., 2014].

Other names

NCR3CD337Natural cytotoxicity triggering receptor 31C7LY117

Activation of natural killer cell-mediated cytotoxicity and pro-inflammatory cytokine release (e.g., IFN-gamma) through ITAM-containing adapter proteins (CD3z or FcERIy) upon binding to tumor-associated ligands such as B7-H6 or BAG6 [UniProt P14770; Brandt et al., 2009].