Nectin-2 and Poliovirus receptor (CD112 and CD155)

Nectin-2 (CD112) and Poliovirus receptor (CD155) are cell surface glycoproteins belonging to the nectin and nectin-like family of the immunoglobulin superfamily. They are frequently overexpressed on various tumor cells, including solid tumors and hematological malignancies, where they play a dual role in modulating the immune microenvironment. These molecules serve as ligands for a network of receptors on T cells and natural killer (NK) cells: the activating receptor CD226 (DNAM-1) and the inhibitory receptors TIGIT and PVRIG (CD112R). In the context of cancer, the overexpression of CD112 and CD155 often favors binding to inhibitory receptors, leading to immune evasion and suppression of anti-tumor effector functions. Therapeutic strategies targeting this axis include monoclonal antibodies against the receptors (e.g., anti-TIGIT, anti-PVRIG), bispecific antibodies, and oncolytic viruses that exploit CD155 for tumor entry. Blocking these interactions aims to restore the balance toward CD226-mediated activation, thereby enhancing the immune system's ability to recognize and eliminate cancer cells. Additionally, certain kinase inhibitors have been shown to downregulate the expression of these ligands, further sensitizing tumors to immune attack.

Other names

CD112CD155PVRL2PVRNectin-2Poliovirus receptorNecl-5PRR2HVEBPVRR2Tage4

Immune checkpoint inhibition by blocking inhibitory signals from TIGIT and PVRIG; restoration of DNAM-1 (CD226) mediated co-stimulation; oncolytic viral therapy via direct tumor entry and lysis; and downregulation of ligand expression through kinase inhibition.