Natural cytotoxicity receptors and DNAX accessory molecule-1 (DNAM-1) (NCRs/DNAM-1)

Natural cytotoxicity receptors (NCRs), including NKp46, NKp44, and NKp30, along with DNAX accessory molecule-1 (DNAM-1/CD226), are critical activating receptors expressed on the surface of cytokine-induced killer (CIK) cells and natural killer (NK) cells. These receptors mediate the recognition and elimination of tumor cells by binding to specific ligands that are often upregulated on the surface of malignant cells, such as CD155 (PVR) and CD112 (Nectin-2) for DNAM-1, and B7-H6 for NKp30. This interaction triggers a signaling cascade that results in the release of cytotoxic granules containing perforin and granzymes, leading to MHC-unrestricted lysis of the target tumor cells. In the context of CIK cell therapy, the expression and functionality of these receptors are vital for the therapeutic efficacy against various hematological and solid tumors. Therapeutic strategies often focus on enhancing the expression of these receptors or preventing their downregulation by the tumor microenvironment to sustain potent anti-tumor immune responses.

Other names

NCRNKp46NKp44NKp30CD226NCR1NCR2NCR3DNAX accessory molecule-1

Activation of cytotoxic immune cells (CIK cells, NK cells) upon binding to tumor-associated ligands such as CD155 (PVR), CD112 (Nectin-2), and B7-H6, leading to MHC-unrestricted tumor cell lysis.