Natural cytotoxicity triggering receptor 3 (NCR3) (NKp30)

Natural cytotoxicity triggering receptor 3 (NCR3), commonly known as NKp30, is a potent activating receptor expressed on natural killer (NK) cells and certain T cell subsets (UniProt O14931). It plays a critical role in tumor immunosurveillance by recognizing specific ligands, most notably B7-H6 (NCR3LG1), which is frequently overexpressed on the surface of various hematologic and solid tumors while remaining largely absent from healthy tissues (PubMed: 21742971). In the context of cytokine-induced memory-like (CIML) NK cells—which are generated through brief ex vivo activation with IL-12, IL-15, and IL-18—NKp30 expression is often maintained or enhanced, contributing to the superior anti-tumor effector functions and longevity of these cells (PubMed: 33613465). Therapeutic strategies leveraging this axis include the adoptive transfer of CIML-NK cells, the development of chimeric antigen receptor (CAR) NK cells incorporating NKp30 signaling domains, and bispecific engagers designed to bridge NKp30-positive cells with B7-H6-expressing tumor targets. These approaches aim to overcome tumor immune evasion and provide a robust, targeted cytotoxic response against malignancies such as acute myeloid leukemia and various carcinomas.

Other names

NKp30CD337Natural killer cell p30-related protein1C7LY117NCR3

Activation of NK cell effector functions through the binding of the NKp30 receptor to B7-H6 ligands on tumor cells, triggering ITAM-mediated signaling that leads to degranulation and the release of perforin and granzymes.