DNAX accessory molecule-1 – Poliovirus receptor interaction (DNAM-1 – PVR/CD155)

The DNAX accessory molecule-1 (DNAM-1), also known as CD226, is a potent activating receptor expressed on the surface of Natural Killer (NK) cells and cytotoxic T cells. It primarily interacts with the Poliovirus receptor (PVR), also known as CD155, which is a cell adhesion molecule frequently overexpressed in various malignancies. This interaction triggers the release of cytotoxic granules and proinflammatory cytokines like IFN-gamma, facilitating the immune-mediated destruction of tumor cells. However, the DNAM-1 – PVR axis is part of a complex regulatory network where PVR also binds to inhibitory receptors such as TIGIT and CD96 with higher affinity, often leading to immune evasion in the tumor microenvironment. Chronic exposure to high levels of CD155 can lead to the downregulation and internalization of DNAM-1, rendering immune cells exhausted or dysfunctional. Consequently, this axis has become a significant focus for cancer immunotherapy, with strategies aiming to block inhibitory competitors or enhance DNAM-1 signaling to restore anti-tumor immunity.

Other names

CD226 – CD155 axisDNAM1 – PVR axisTLiSA1 – Necl-5 interactionCD226 – Poliovirus receptor interaction

Antagonism of inhibitory receptors (TIGIT/PVRIG) to favor DNAM-1 binding; Agonism of DNAM-1 to enhance cytotoxicity; Oncolytic viral entry via CD155; Blockade of CD155 to inhibit tumor cell migration.