Emerging treatment options for nasopharyngeal carcinoma
PD‑1/PD‑L1 inhibitors combined with chemotherapy significantly improve survival in recurrent/metastatic nasopharyngeal carcinoma, while persistent challenges include resistance mechanisms, biomarker validation, and treatment optimization
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.
The review highlights that PD‑1/PD‑L1 inhibitors combined with chemotherapy significantly improve survival in recurrent/metastatic nasopharyngeal carcinoma, while persistent challenges include resistance mechanisms, biomarker validation, and treatment optimization.
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