Natural cytotoxicity-triggering receptor 3 (NCR3)

Natural cytotoxicity-triggering receptor 3 (NCR3), also known as NKp30 or CD337, is a pivotal activating receptor constitutively expressed on the surface of Natural Killer (NK) cells and certain T cell subsets [6, 19]. It belongs to the natural cytotoxicity receptor family within the immunoglobulin superfamily and functions as a primary sensor for identifying stressed, virally infected, or malignant cells by binding non-MHC ligands such as B7-H6 and BAG6 [9, 13]. Upon engagement, NCR3 signals through ITAM-containing adaptors like CD3-zeta to trigger NK cell degranulation, the release of cytotoxic granules, and the production of pro-inflammatory cytokines such as IFN-gamma and TNF-alpha [13, 17]. Beyond direct cytotoxicity, NCR3 is essential for the crosstalk between NK cells and dendritic cells, promoting dendritic cell maturation and coordinating the innate-to-adaptive immune transition [14, 17]. In clinical contexts, dysregulation of NCR3 expression or the presence of soluble inhibitory ligands (e.g., sB7-H6) is often associated with tumor immune evasion and poor prognosis in various cancers, including neuroblastoma and gastrointestinal stromal tumors [1, 7, 8]. Consequently, NCR3 is a prominent therapeutic target for next-generation immunotherapies, including bispecific NK-cell engagers (NKCEs) and chimeric antigen receptor (CAR) therapies designed to redirect NK cell activity toward tumor-associated antigens [11, 15].

Other names

NKp30CD337Natural killer cell p30-related protein1C7LY117MALSActivating natural killer receptor p30

Agonism of natural killer cell activating receptors to induce tumor cell lysis; recruitment of NK cells to tumor-associated antigens through bispecific engagement.