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Nectin and Nectin-like Binding Receptors and Ligands

Natural killer (NK) cells and CD8+ T cells express the nectin and nectin-like binding receptors, DNAM-1/CD226, TIGIT, CRTAM, and CD96. DNAM-1/CD226 and TIGIT both bind to CD112/Nectin-2 and CD155/PVR, two proteins that are frequently up-regulated on tumor cells, but they have opposing effects on NK cell activity. DNAM-1/CD22 is expressed on resting NK cells and promotes NK cell activation, while TIGIT expression is elevated following NK cell activation and negatively regulates NK cell cytotoxicity. Additionally, CD96 competes with DNAM-1/CD226 for binding to CD155/PVR and inhibits IFN-gamma production by NK cells, suggesting that blockade of the interactions between TIGIT and CD155/PVR and/or CD96 and CD155/PVR may have beneficial anti-tumor effects. As preliminary research has revealed the complexity of the interactions among these receptors and their involvement in tumor surveillance, the effects of these receptors on NK cells warrant further investigation.