Epstein‑Barr virus reprograms immune escape in nasopharyngeal carcinoma

Rákkutatás · Nasopharyngeal carcinoma

Epstein‑Barr virus drives immune escape in nasopharyngeal carcinoma by reprogramming the tumor immune microenvironment—activating NF‑κB and JAK‑STAT pathways, up‑regulating multiple immune checkpoints (PD‑L1, TIM‑3, LAG‑3, TIGIT) and recruiting suppressive myeloid cells—thereby diminishing the efficacy of anti‑PD‑1 therapies and providing a rationale for combination immunotherapies that target both viral signaling and host immune checkpoints.

Nasopharyngeal carcinoma (NPC) is an Epstein Fr-as–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.

NPC is a leading cause of cancer mortality in southern China and Southeast Asia, yet its unique EBV‑driven immune escape renders conventional immunotherapies largely ineffective. Understanding the mechanisms by which EBV reprograms the tumor microenvironment can identify novel targets for combination therapies, improve patient stratification, and ultimately enhance survival rates.

Bizonyítékszint: Sejtvonalas. Laboratóriumi sejtekben vizsgálták.

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