Harnessing the immune microenvironment: advances in nasopharyngeal carcinoma immunotherapy

Nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-driven malignancy with distinct geographic prevalence, presents as locally advanced or metastatic disease in over 70% of patients. Its unique tumor microenvironment (TME) exhibits dense immune infiltration paradoxically coupled with profound immunosuppression orchestrated by EBV through PD-L1 induction, antigen presentation disruption, immunosuppressive cell recruitment, and extracellular vesicle exploitation. These mechanisms underpin the rationale for immunotherapy, where PD-1/PD-L1 inhibitors have transformed management: phase III trials established PD-1 blockade combined with chemotherapy as first-line standard for recurrent/metastatic NPC, significantly improving survival, while integration into locoregionally advanced disease regimens enhances response rates and outcomes. Novel bispecific antibodies and rational combinations (with radiotherapy, anti-angiogenics, and EBV-targeted therapies) show promise in overcoming resistance. Biomarker advances extend beyond PD-L1 to include radiomics, AI-driven models, liquid biopsy markers (EBV-DNA dynamics, exosomal CA1), and tissue-based features (tertiary lymphoid structures, CD70/CD27 axis). Persistent challenges encompass EBV-mediated resistance, biomarker validation, and therapeutic optimization. This review comprehensively synthesizes the mechanistic basis of NPC immune evasion, clinical progress across diverse immunotherapies, biomarker-driven precision strategies, and emerging approaches to harness the immune microenvironment for improved patient outcomes.