NECTIN2 (nectin cell adhesion molecule 2) is a cell adhesion molecule that functions as an immune checkpoint ligand with critical roles in viral infection and cancer immunosuppression. Mechanistically, NECTIN2 binds to TIGIT, an inhibitory receptor expressed on T cells and natural killer cells, transducing immunosuppressive signals that promote immune cell exhaustion and dysfunction 1. NECTIN2 is expressed by diverse cell populations including tumor-associated neutrophils, cancer-associated fibroblasts, and dendritic cells within the tumor microenvironment, where it suppresses anti-tumor immunity 23. Additionally, NECTIN2 serves as a receptor for herpesviruses (HSV-1 and HSV-2), facilitating viral entry into host cells [UniProt Function]. In disease contexts, elevated NECTIN2 expression correlates with poor prognosis across multiple cancers including ovarian cancer, neuroblastoma, pancreatic cancer, colorectal cancer, hepatocellular carcinoma, and breast cancer metastases 456378. Clinically, NECTIN2-TIGIT axis blockade represents a promising immunotherapeutic strategy; dual TIGIT and PD-L1 blockade demonstrated complete tumor regression in neuroblastoma models and showed predictive value for checkpoint blockade response in ovarian cancer 54. Targeting NECTIN2 directly enhances CD8+ T cell function and improves immunotherapy efficacy in pancreatic cancer 2.