Classic Hodgkin lymphoma (cHL) in patients with immune deficiency/dysregulation represents a critical unmet need in hematology, demanding the appropriate revision of classification and therapeutic paradigms. Epstein–Barr virus (EBV) is a pivotal driver of lymphomagenesis in this high-risk subset, where viral oncoproteins (e.g., LMP1/2A) exploit immune vulnerabilities to activate NF-κB, rewire tumor microenvironments (TME), and evade immune surveillance. EBV-positive cHL, prevalent in immunosuppressed populations, exhibits distinct molecular hallmarks, including reduced somatic mutations, unique HLA associations, and profound PD-L1-mediated immune suppression, that diverge from EBV-negative cases reliant on genetic aberrations. Despite advances in combined antiretroviral therapy, HIV co-infection exacerbates pathogenesis, M2 macrophage dominance, and T-cell exhaustion, while links to other viruses remain ambiguous. Current therapies fail to adequately target these viral and immune complexities, leaving patients with poorer outcomes. This review synthesizes insights into EBV’s etiological role, immune contexture disparities, and the genetic–environmental interplay shaping cHL heterogeneity. The WHO classification highlights the need to reclassify EBV-associated cHL as a distinct subset, integrating viral status and immune biomarkers into diagnostic frameworks. Urgent priorities include global epidemiological studies to clarify causal mechanisms, development of virus-targeted therapies (e.g., EBV-specific T-cell strategies, PD-1/CTLA-4 blockade), and personalized regimens for immune-dysregulated cohorts.
免疫缺陷/失调患者的经典霍奇金淋巴瘤（cHL）是血液学领域亟待解决的关键难题，亟需对现有分类体系及治疗范式进行适当修订。爱泼斯坦-巴尔病毒（EBV）是这一高危亚群淋巴瘤发生的关键驱动因素，其病毒癌蛋白（如LMP1/2A）通过利用免疫缺陷激活NF-κB通路、重塑肿瘤微环境并逃避免疫监视。在免疫抑制人群中高发的EBV阳性cHL呈现出独特的分子特征，包括体细胞突变减少、特异性HLA关联以及显著的PD-L1介导的免疫抑制，这些特征与依赖遗传异常的EBV阴性病例存在本质差异。尽管联合抗逆转录病毒治疗取得进展，但HIV共感染仍会加剧疾病进展、促进M2巨噬细胞优势分化及T细胞耗竭，而与其他病毒的关联尚不明确。现有疗法未能有效针对这些病毒与免疫的复杂相互作用，导致患者预后较差。本综述系统阐述了EBV的致病机制、免疫微环境差异以及遗传-环境交互作用如何塑造cHL异质性。世界卫生组织分类标准强调需将EBV相关cHL重新界定为独立亚型，并将病毒状态与免疫生物标志物整合至诊断体系。当前紧迫任务包括：开展全球流行病学研究以阐明致病机制、研发病毒靶向疗法（如EBV特异性T细胞策略、PD-1/CTLA-4阻断剂），并为免疫失调人群制定个体化治疗方案。
Immune Deficiency/Dysregulation-Associated EBV-Positive Classic Hodgkin Lymphoma
肿瘤(癌症)患者之家