Epstein–Barr virus (EBV) contributes to oncogenesis and immune evasion in nasopharyngeal carcinoma (NPC). At present, an aggregated, higher-level view on the impact of EBV genes toward the immune microenvironment of NPC is lacking. To this end, we have interrogated tumor-derived RNA sequences of 106 treatment-naive NPC patients for 98 EBV transcripts, and captured the presence of 10 different immune cell populations as well as 23 different modes of T-cell evasion. We discovered 3 clusters of EBV genes that each associate with distinct immunophenotypes of NPC. Cluster 1 associated with gene sets related to immune cell recruitment, such as those encoding for chemoattractants and their receptors. Cluster 2 associated with antigen processing and presentation, such as interferon-related genes, whereas cluster 3 associated with presence of M1-like macrophages, absence of CD4+ T cells, and oncogenic pathways, such as the nuclear factor kappa light-chain enhancer of activated B-cell pathway. We discuss these 3 EBV clusters regarding their potential for stratification for T-cell immunity in NPC together with the next steps needed to validate such therapeutic value.

EB 病毒 (EBV) 有助于鼻咽癌 (NPC) 的肿瘤发生和免疫逃避。目前，缺乏关于 EBV 基因对鼻咽癌免疫微环境影响的综合、更高层次的观点。为此，我们对 106 名初治鼻咽癌患者的肿瘤来源 RNA 序列进行了询问，以获取 98 个 EBV 转录本，并捕获了 10 种不同免疫细胞群的存在以及 23 种不同的 T 细胞逃避模式。我们发现了 3 个 EBV 基因簇，每个簇都与 NPC 的不同免疫表型相关。簇 1 与与免疫细胞募集相关的基因集相关，例如编码化学引诱剂及其受体的基因集。簇 2 与抗原加工和呈递相关，例如干扰素相关基因，而簇 3 与 M1 样巨噬细胞的存在、CD4+ T 细胞的缺乏和致癌途径相关，例如激活的核因子 kappa 轻链增强子B 细胞途径。我们讨论了这 3 个 EBV 簇在 NPC 中 T 细胞免疫分层的潜力，以及验证此类治疗价值所需的后续步骤。