Epstein–Barr virus reprograms immune escape in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is an Epstein - Barr virus (EBV)-associated epithelial malignancy characterized by an immune-rich yet immunosuppressive microenvironment. EBV establishes an inflammatory but immune-tolerant ecosystem that underlies poor responses to immunotherapy. While prior studies have focused on single checkpoints such as PD-1/PD-L1, they often overlook the systemic immune reprogramming driven by EBV. Viral latent proteins, particularly LMP1, activate NF-κB and JAK - STAT signaling, inducing cytokine production, immune cell reeducation, and therapeutic resistance. This leads to upregulation of multiple checkpoint molecules, T-cell dysfunction, myeloid suppression, and immune exclusion. Consequently, anti-PD-1 therapies show limited efficacy, as tumors exploit alternative checkpoints (e.g. TIM-3, LAG-3, TIGIT) and stromal barriers. This review comprehensively summarizes EBV-driven immune remodeling in NPC and highlights emerging therapeutic strategies targeting both host immunity and EBV-associated signaling axes to overcome immune escape, enhance immunotherapy efficacy, and ultimately improve clinical outcomes.