PVRIG (PVR related immunoglobulin domain containing) is a coinhibitory immune checkpoint receptor that suppresses T-cell and NK cell-mediated antitumor immunity. The receptor specifically binds to PVRL2 (CD112/Nectin-2) and competes with the activating receptor CD226 for ligand binding 1. Upon interaction with PVRL2, PVRIG inhibits T-cell proliferation and cytokine production, representing a nonredundant signaling pathway distinct from other checkpoint receptors like TIGIT 1. PVRIG is highly expressed on tumor-infiltrating NK cells and CD8+ T cells with exhausted phenotypes across multiple cancer types 2. The receptor plays a crucial role in tumor immune evasion, with elevated expression observed in various malignancies including endometrial, ovarian, and colorectal cancers 13. Therapeutically, PVRIG blockade unleashes antitumor immunity by reversing immune cell exhaustion and enhancing cytotoxic function 2. Combination strategies targeting PVRIG alongside other checkpoint inhibitors like PD-1, PD-L1, or TIGIT demonstrate enhanced therapeutic efficacy compared to single-agent approaches 41. These findings position PVRIG as a promising target for cancer immunotherapy, particularly for patients with checkpoint inhibitor-resistant tumors.