PVR (poliovirus receptor, CD155) is a cell adhesion molecule that functions as a critical immune checkpoint regulator with dual roles in immune activation and suppression. As a ligand for multiple receptors on effector lymphoid cells, PVR binding to DNAM-1 promotes T and NK cell cytotoxicity 1, while its engagement with inhibitory receptors TIGIT and CD96 suppresses anti-tumor immunity and promotes immune escape 2. PVR is highly expressed on tumor cells and antigen-presenting cells across multiple malignancies, including gynecological and solid tumors, where it correlates with reduced effector infiltration and inferior prognosis 3. Recent evidence demonstrates that PVR exposure downregulates expression of its receptors (DNAM-1, TIGIT, CD96) on CD8+ T cells and can be transferred to T cells via CD96-mediated mechanisms, further dampening anti-tumor responses 4. The PVR-TIGIT/CD96/DNAM-1 axis represents a promising immunotherapy target, with therapeutic approaches including checkpoint blockade via monoclonal antibodies, bispecific engagers, and CAR-modified T/NK cells showing efficacy in preclinical models 2. Understanding PVR's complex immunomodulatory mechanisms is essential for developing next-generation cancer immunotherapies to overcome resistance to current checkpoint inhibitors 5.