Poliovirus receptor (PVR, CD155), a member of the nectin-like family of proteins, is recently emerging as a promising target in immunotherapy that enhances the existing anti-tumor responses. Similar to other members of the family, PVR is involved in important cellular processes, such as adhesion, contact inhibition, migration, proliferation, and the immune response [PMID: 18648374]. PVR is dramatically overexpressed in several human malignancies, whereas its expression is low or absent in most healthy tissues [PMID: 10841575, PMID: 11454801, PMID: 15604290, PMID: 15536144, PMID: 19801517]. Consistent with PVR biology, its overexpression promotes tumor cell invasion, migration, and proliferation and is associated with a poor prognosis and enhanced tumor progression [PMID: 16322240, PMID: 17893876, PMID: 25743219, PMID: 25862891]. Simultaneously, PVR has a considerable immunoregulatory potential. It interacts with the (co)stimulatory receptor DNAM-1 and the inhibitory receptors TIGIT and CD96, resulting in either immune cell activation or inhibition, respectively [PMID: 28870470].