The Epstein-Barr Virus (EBV) in T Cell and NK Cell Lymphomas: Time for a Reassessment.
The Epstein-Barr Virus (EBV) in T Cell and NK Cell Lymphomas: Time for a Reassessment.
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DOI：
10.1007/s11899-015-0292-z
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发表时间：
2015-12
影响因子：
2.9
通讯作者：
Porcu P
中科院分区：
文献类型：
--
作者：
Gru AA;Haverkos BH;Freud AG;Hastings J;Nowacki NB;Barrionuevo C;Vigil CE;Rochford R;Natkunam Y;Baiocchi RA;Porcu P
虽然EB病毒（EBV）最初被发现并表征为B细胞肿瘤中的致癌病毒，但它在T/NK细胞淋巴瘤中也起着复杂和多方面的作用。在B细胞淋巴瘤中，已显示EBV编码的蛋白质通过刺激NF-κB途径和增加抗凋亡基因的表达直接促进永生化和增殖。在成熟T/NK淋巴瘤（MTNKL）的背景下，除了结节性NK/T细胞淋巴瘤（ENKTL）可能例外，该病毒可能发挥更多样化和微妙的作用。EBV已被证明通过促进Th 2偏斜的T细胞应答和通过增加免疫检查点配体PD-L1的表达来塑造肿瘤微环境。感染细胞的类型、血浆EBV DNA的量和病毒裂解复制的程度都被认为对T/NK细胞淋巴瘤具有预后价值。已经使用EBV感染的B细胞模型定义了EBV感染的潜伏模式，并且尚未在T/NK细胞淋巴瘤中明确建立。确定EBV裂解蛋白的表达谱可以允许使用抗病毒药物进行个体化治疗。需要做更多的工作来确定EBV相关的MTNKL是否具有独特的生物学和临床特征，这些特征可以用于风险分层，疾病监测和治疗目的。
While Epstein-Barr virus (EBV) was initially discovered and characterized as an oncogenic virus in B cell neoplasms, it also plays a complex and multifaceted role in T/NK cell lymphomas. In B cell lymphomas, EBV-encoded proteins have been shown to directly promote immortalization and proliferation through stimulation of the NF-κB pathway and increased expression of anti-apoptotic genes. In the context of mature T/NK lymphomas (MTNKL), with the possible exception on extranodal NK/T cell lymphoma (ENKTL), the virus likely plays a more diverse and nuanced role. EBV has been shown to shape the tumor microenvironment by promoting Th2-skewed T cell responses and by increasing the expression of the immune checkpoint ligand PD-L1. The type of cell infected, the amount of plasma EBV DNA, and the degree of viral lytic replication have all been proposed to have prognostic value in T/NK cell lymphomas. Latency patterns of EBV infection have been defined using EBV-infected B cell models and have not been definitively established in T/NK cell lymphomas. Identifying the expression profile of EBV lytic proteins could allow for individualized therapy with the use of antiviral medications. More work needs to be done to determine whether EBV-associated MTNKL have distinct biological and clinical features, which can be leveraged for risk stratification, disease monitoring, and therapeutic purposes.