Natural cytotoxicity receptor 3 (NKp30)

Natural cytotoxicity receptor 3 (NKp30, also known as NCR3 or CD337) is a type I transmembrane protein expressed predominantly on natural killer (NK) cells, where it serves as a major activating receptor for the recognition and lysis of tumor and infected cells. The best-characterized ligand for NKp30 is B7-H6, a member of the B7 family, which is selectively expressed on a broad spectrum of tumor cells but not on normal tissues. When NKp30 on NK cells engages its ligand (e.g., B7-H6) on a target cell, it triggers NK cell activation via association with ITAM-containing adaptor proteins (mainly CD3ζ and FcRγ), leading to cytotoxic granule release and cytokine production. Tumors can evade NKp30-mediated killing by shedding ligands (e.g., soluble B7-H6, soluble BAG-6/BAT3), thereby impairing NK cell activation and contributing to immune escape. The pathway is an attractive immunotherapeutic target, but clinical translation is challenged by limited ligand specificity, tumor-mediated immune suppression, and a lack of highly specific drugs directly targeting NKp30 interactions[1][2][3][4][5][6][7][8].

Other names

NCR3NKp30CD337

Activation of NK cells by ligand binding triggers cytotoxic granule release, cytokine production, and direct killing of ligand-expressing tumor cells. Ligand shedding (as soluble B7-H6 or BAG-6) can inhibit NKp30-mediated activation and promote tumor immune escape.