CD226 antigen (DNAX accessory molecule 1) receptor (DNAM-1)

CD226, commonly known as DNAX Accessory Molecule-1 (DNAM-1), is a type I transmembrane glycoprotein and a member of the immunoglobulin superfamily expressed on natural killer (NK) cells, CD8+ T cells, and other immune subsets (UniProt P32942). It functions as a critical activating receptor that promotes immune surveillance by binding to its ligands, CD155 (PVR) and CD112 (Nectin-2), which are frequently overexpressed on the surface of various tumor cells (PubMed 31434705). Upon ligand binding, DNAM-1 triggers intracellular signaling pathways that enhance NK cell-mediated cytotoxicity and T cell proliferation and cytokine production. In the context of cancer, this interaction is often impaired because inhibitory receptors such as TIGIT and CD96 compete for the same ligands with higher affinity, leading to immune evasion (PubMed 28636011). Therapeutic strategies primarily involve using monoclonal antibodies to block these inhibitory competitors, thereby "releasing" the ligands to bind DNAM-1 and restore anti-tumor immunity. Additionally, the expression levels of DNAM-1 and its ligands serve as important biomarkers for predicting response to checkpoint inhibitor therapies (PubMed 33011214).

Other names

CD226DNAX accessory molecule 1DNAM1PTA1TLiSA1

Restoration of DNAM-1 (CD226) costimulatory signaling through the blockade of competing inhibitory receptors (TIGIT, PVRIG, CD96) that share the same ligands (CD155, CD112).