Poliovirus receptor (CD155) and Nectin cell adhesion molecule 2 (CD112) (CD155 and CD112)

Poliovirus receptor (CD155) and Nectin-2 (CD112) are cell surface glycoproteins belonging to the immunoglobulin superfamily that serve as the primary ligands for the DNAM-1 (CD226) activating receptor on NK cells and T cells [UniProt P15151, Q92692]. In healthy tissues, these molecules mediate cell-cell adhesion and provide costimulatory signals essential for immune surveillance [He et al., 2021]. However, many malignancies overexpress CD155 and CD112 to exploit the inhibitory checkpoint signaling of receptors like TIGIT and PVRIG, which bind these ligands with significantly higher affinity than DNAM-1 [Compugen, 2023]. This competitive binding effectively outcompetes the activating DNAM-1 signal, leading to immune evasion, T cell exhaustion, and tumor progression within the microenvironment [PubMed 30305468]. Therapeutic strategies targeting this axis include monoclonal antibodies that block the inhibitory receptors or directly target the ligands, such as OR2805, to restore DNAM-1-mediated anti-tumor immunity [OncoResponse, 2023]. By shifting the balance back toward activation, these agents aim to enhance the ability of the immune system to recognize and eliminate cancer cells [He et al., 2021].

Other names

PVRNectin-2PVRL2Necl-5HveBCD226 ligandsDNAM-1 ligands

Blockade of the interaction between tumor-expressed ligands (CD155/CD112) and inhibitory receptors (TIGIT/PVRIG) to restore DNAM-1-mediated immune activation.