DNAX accessory molecule-1 ligand (commonly: Poliovirus receptor and Nectin-2 as individual ligands) (null)

The DNAM-1 pathway is a critical axis for immune recognition and elimination of tumor and virus-infected cells. DNAX accessory molecule-1 (DNAM-1, CD226) is an activating receptor found on NK cells and cytotoxic T lymphocytes. Its main ligands, Poliovirus receptor (CD155, PVR) and Nectin-2 (CD112, PVRL2), are cell surface proteins upregulated on many solid and hematologic cancer cells, as well as stressed or infected cells. Recognition of these ligands by DNAM-1 promotes immune cell cytotoxicity and cytokine secretion, contributing to tumor immunosurveillance. Some cancer therapies aim to exploit this axis, for example by using DNAM-1-based CAR-NK cells or by blocking inhibitory receptors (such as TIGIT) that compete with DNAM-1 for ligand binding. Loss or reduced expression of these ligands, or their masking by soluble forms, represents a mechanism of immune escape by tumors[1][2][3][5][7].

Other names

DNAM-1 ligandCD155 (Poliovirus receptor, PVR)CD112 (Nectin-2, PVRL2)DNAM-1 ligands

Immune checkpoint modulation (e.g., anti-TIGIT antibodies block inhibitory signals, tipping balance towards DNAM-1-mediated activation) Adoptive cell therapy (e.g., DNAM-1 chimeric antigen receptor-NK cells target ligand-expressing tumors)