Nectin-1 (Poliovirus receptor-related 1) and Nectin-4 (Poliovirus receptor-related 4), and Herpesvirus entry mediator (HVEM; also known as TNFRSF14) (Nectin-1 (PVRL1); Nectin-4 (PVRL4); HVEM (TNFRSF14))

Nectins are a family of immunoglobulin-like cell adhesion molecules, with Nectin-1 (PVRL1) and Nectin-4 (PVRL4) as principal members involved in cell-cell adhesion, tissue architecture, and as entry receptors for viruses such as herpes simplex virus (Nectin-1) and measles virus (Nectin-4)[2][6]. Nectin-4 is highly upregulated in several epithelial cancers, supporting tumor growth, invasion, angiogenesis, and immune evasion, partly through its interaction with the immune checkpoint receptor TIGIT and the PI3K/AKT pathway[1][3]. HVEM (TNFRSF14) is a member of the tumor necrosis factor receptor superfamily, broadly expressed in lymphoid and peripheral tissues, acting as both an immune modulator and an alternative entry receptor for herpes simplex virus, with a role in tumor immunology and viral pathogenesis[2][4]. Both Nectin-4 and HVEM are being explored as therapeutic targets in cancer and infectious disease, and their expression patterns are being leveraged for targeted therapy and as biomarkers in oncology.

Other names

Herpesvirus entry mediator C (HveC)CD111PVRL1PVRL4Poliovirus receptor-like 4Herpesvirus entry mediatorTNFRSF14HveA

Antibody–drug conjugated cytotoxicity (e.g., Enfortumab vedotin binds Nectin-4, delivers MMAE toxin to cancer cells) Oncolytic virotherapy (engineered viruses use Nectin-4 for selective tumor cell entry and lysis) Viral entry blockade (inhibition of HSV gD interaction with Nectin-1 or HVEM impedes viral infection) Immune checkpoint modulation (drugs inhibiting Nectin-4/TIGIT signaling restore immune response against tumors)