文章：

爱泼斯坦-巴尔病毒感染、霍奇金淋巴瘤与免疫系统：免疫逃逸分子机制研究进展

Epstein–Barr Infection, Hodgkin’s Lymphoma, and the Immune System: Insights into the Molecular Mechanisms Facilitating Immune Evasion

原文发布日期：28 April 2025

DOI: 10.3390/cancers17091481

类型: Article

开放获取: 是

英文摘要：

Epstein–Barr virus (EBV) constitutes a very common pathogen and a well-characterized carcinogen. EBV has the ability to establish a chronic latent infection, during which only a subset of the viral genes is expressed. EBV is implicated in multiple malignancies, including Hodgkin’s lymphoma (HL). HL mainly affects adolescents and young adults and has an overall favorable prognosis. However, relapsed or refractory disease still poses a therapeutic challenge. EBV does not only induce malignant transformation but also hinders the detection and clearance of the neoplastic cells by the immune system. The proteins and non-coding RNAs expressed in latency IIa, which is associated with HL, employ a variety of mechanisms to target different steps of innate and adaptive immunity, to take advantage of the immunosuppressant effect of immune checkpoints, and to shape the microenvironment to support the survival and proliferation of malignant cells. They suppress the expression or promote the degradation of pattern-recognition receptors, interfere with type I interferon and proinflammatory cytokine mediated signaling, and hinder the effector function of natural killer cells. The processing and presentation of peptides to CD4 and CD8 T cells are also hampered. EBV induces the expression of immune checkpoints, the secretion of immunosuppressive cytokines, and the efflux of regulatory T cells in the tumor microenvironment. The current review provides a comprehensive overview of the molecular mechanisms underlying this complex interplay between EBV and the immune system in HL with focus on clinical data from the pediatric population, which is the key for developing novel, effective therapeutic interventions.

摘要翻译： 

爱泼斯坦-巴尔病毒（EBV）是一种极为常见的病原体，也是特征明确的致癌因子。该病毒能够建立慢性潜伏感染，期间仅表达部分病毒基因。EBV与多种恶性肿瘤的发生相关，其中包括霍奇金淋巴瘤（HL）。HL主要累及青少年及年轻成人群体，总体预后良好，但复发或难治性病例仍是临床治疗面临的挑战。EBV不仅能够诱导恶性转化，还会阻碍免疫系统对肿瘤细胞的识别与清除。在HL相关的IIa型潜伏感染中，病毒表达的蛋白与非编码RNA通过多种机制靶向先天性与适应性免疫的不同环节：既利用免疫检查点的免疫抑制效应，又重塑微环境以支持恶性细胞的存活与增殖。这些病毒产物可抑制模式识别受体的表达或促进其降解，干扰I型干扰素及促炎细胞因子介导的信号传导，并阻碍自然杀伤细胞的效应功能。同时，CD4与CD8 T细胞的抗原肽加工呈递过程也受到抑制。EBV还能诱导肿瘤微环境中免疫检查点的表达、免疫抑制性细胞因子的分泌以及调节性T细胞的浸润。本综述系统阐述了HL中EBV与免疫系统复杂相互作用的分子机制，重点关注儿童群体的临床数据，这为开发新型有效治疗策略提供了关键依据。

原文链接：

Epstein–Barr Infection, Hodgkin’s Lymphoma, and the Immune System: Insights into the Molecular Mechanisms Facilitating Immune Evasion