Epstein-Barr virus-driven immunosuppression in nasopharyngeal carcinoma: a comprehensive review of viral mechanisms, spatial tumor ecosystems, and precision therapeutics
Abstract
Background: EBV infection is the defining etiological factor in nasopharyngeal carcinoma (NPC), yet how viral factors systematically remodel the tumor immune microenvironment (TME) to sustain immunosuppression remains incompletely characterized. Existing reviews lack an integrated synthesis of viral mechanisms, TME spatial architecture, and therapeutic translation.
Methods: We conducted a comprehensive literature search across PubMed, Embase, and Web of Science from inception to December 2025, with an update check to May 2026, following PRISMA guidelines. Given the broad scope, a narrative synthesis was adopted rather than a formal systematic review. Two reviewers independently screened 4,235 records, and 182 studies were included. Methodological quality was assessed using Cochrane RoB 2 and Newcastle-Ottawa tools, with detailed risk-of-bias summaries provided in the Supplementary Materials.
Results: EBV establishes hierarchical immunosuppression in NPC. Latent proteins LMP1, LMP2A, and EBNA1, together with non-coding RNAs (BART miRNAs, EBERs), constitutively activate NF-κB, PI3K/AKT/mTOR, and JAK/STAT pathways; LMP1 further promotes exosomal secretion and metabolic reprogramming that expands myeloid-derived suppressor cells. Lytic-phase genetic polymorphisms in BALF2, BZLF1, and BRLF1 are associated with differential immune signatures, though these associations remain correlative and lack functional validation. Based on limited spatial profiling studies, the TME can be…
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