CD226 (DNAX accessory molecule-1) (CD226)

CD226, commonly known as DNAX accessory molecule-1 (DNAM-1), is a 65 kDa type I transmembrane glycoprotein belonging to the immunoglobulin superfamily [1]. It is constitutively expressed on the surface of natural killer (NK) cells, CD8+ T cells, and other immune subsets, where it functions as a potent activating receptor [2]. CD226 mediates cellular adhesion and triggers effector functions, such as cytokine production and cytotoxicity, upon binding to its primary ligands, CD155 (PVR) and CD112 (Nectin-2), which are frequently overexpressed on tumor cells [3][4]. In the tumor microenvironment, the CD226 signaling pathway is often suppressed by the upregulation of inhibitory receptors like TIGIT and PVRIG, which compete for the same ligands with higher affinity, effectively shielding the ligands from CD226 and leading to immune evasion [5]. Current therapeutic strategies focus on blocking these inhibitory checkpoints to favor the interaction between endogenous CD226 and its ligands, thereby restoring the anti-tumor activity of NK and T cells [6]. Beyond oncology, CD226 is a significant factor in autoimmune diseases, with genetic variants linked to increased susceptibility to conditions such as multiple sclerosis and type 1 diabetes [7].

Other names

DNAM-1DNAX accessory molecule-1PTA1TLiSA1CD226 antigenPlatelet and T cell activation antigen 1

Restoration of CD226-mediated activating signals by blocking competing inhibitory receptors (TIGIT, PVRIG) or directly modulating the CD226-ligand axis to enhance anti-tumor immunity.