Cluster of differentiation 226 ligands (CD226L)

CD226 ligands, primarily comprising CD155 (Poliovirus receptor, PVR) and CD112 (Nectin-2), are cell surface glycoproteins belonging to the immunoglobulin superfamily that play a pivotal role in regulating immune cell activity (PubMed: 30804956). These ligands interact with a complex network of receptors on T cells and natural killer (NK) cells, known as the DNAM-1/TIGIT/PVRIG axis (PubMed: 31611614). Specifically, they bind to the activating receptor CD226 (DNAM-1) to promote immune activation and cytotoxicity, but they also bind with higher affinity to inhibitory receptors such as TIGIT and PVRIG, which suppress immune responses (PubMed: 19448622). In many cancers, CD155 and CD112 are overexpressed, leading to the exhaustion of tumor-infiltrating lymphocytes and immune evasion by favoring inhibitory signaling over CD226-mediated activation (PubMed: 28930664). Therapeutic interventions targeting these ligands, such as monoclonal antibodies like OMP-313M32, aim to disrupt the inhibitory interactions and restore the pro-inflammatory signaling required for effective anti-tumor immunity (PubMed: 30305468).

Other names

DNAM-1 ligandsPoliovirus receptorPVRCD155Nectin-2CD112PVRL2Necl-5

Blocking the interaction of CD155 and CD112 with inhibitory receptors TIGIT and PVRIG to prevent immune suppression, while potentially preserving or enhancing their interaction with the activating receptor CD226 (DNAM-1) to promote anti-tumor T-cell and NK-cell activity.