DNAX accessory molecule-1 (DNAM-1) and Natural cytotoxicity receptor 3 (NKp30) (DNAM-1/NKp30)

DNAX accessory molecule-1 (DNAM-1, CD226) and Natural cytotoxicity receptor 3 (NKp30, NCR3) are key activating receptors constitutively expressed on Natural Killer (NK) cells and Cytokine-Induced Killer (CIK) cells [NIH, 2019; Frontiers in Immunology, 2023]. These receptors mediate the recognition and lysis of tumor cells and virus-infected cells by interacting with specific ligands: DNAM-1 binds to CD155 (PVR) and CD112 (Nectin-2), while NKp30 recognizes B7-H6 and BAG6 (BAT3) [NIH, 2021; MDPI, 2019]. These ligands are often overexpressed on various malignancies and dendritic cells (DCs) under stress, but are largely absent from healthy tissues [Frontiers in Immunology, 2023; NIH, 2013]. Upon engagement, these receptors trigger signaling pathways involving Src kinases and Grb2, leading to the release of cytotoxic granules and the production of interferon-gamma [NIH, 2019; NIH, 2023]. In the tumor microenvironment, the DNAM-1 axis is frequently inhibited by competing receptors such as TIGIT and PVRIG, which bind the same ligands with higher affinity [NIH, 2021; MDPI, 2021]. Therapeutic strategies include the development of checkpoint inhibitors to block these inhibitory interactions and the engineering of CAR-NK or CIK cells to enhance tumor-specific activation [Frontiers in Immunology, 2023; NIH, 2023].

Other names

CD226NCR3CD337DNAX accessory molecule-1Natural killer cell p30-related proteinNatural cytotoxicity receptor 3

Activation of cytotoxic immune cells (NK and CIK cells) through direct ligand engagement or by blocking competing inhibitory receptors (TIGIT, PVRIG) to restore activating signaling [NIH, 2021; Frontiers in Immunology, 2023].