非特指EBV阳性弥漫大B细胞淋巴瘤的研究进展

陈光亮; 吴方恬; 曹军宁

doi:10.19401/j.cnki.1007-3639.2022.03.009

您当前的位置：

首页 >

文章列表页 >

非特指EBV阳性弥漫大B细胞淋巴瘤的研究进展

综述 | 更新时间：2025-12-31

- 非特指EBV阳性弥漫大B细胞淋巴瘤的研究进展
- Advances in research on EBV positive diffuse large B-cell lymphoma, not otherwise specified
- 中国癌症杂志 2022年32卷第3期页码：258-267
- 作者机构：
  
  复旦大学附属肿瘤医院淋巴瘤科,复旦大学上海医学院肿瘤学系,上海 200032
- 作者简介：
  
  曹军宁 E-mail: cao_junning@126.com
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2022.03.009
  中图分类号： R733.1
- 收稿：2021-11-15，
  
  纸质出版：2022-03-30
- 稿件说明：
移动端阅览
陈光亮, 吴方恬, 曹军宁. 非特指EBV阳性弥漫大B细胞淋巴瘤的研究进展[J]. 中国癌症杂志, 2022,32(3):258-267.

Guangliang CHEN, Fangtian WU, Junning CAO. Advances in research on EBV positive diffuse large B-cell lymphoma, not otherwise specified[J]. China Oncology, 2022, 32(3): 258-267.
陈光亮, 吴方恬, 曹军宁. 非特指EBV阳性弥漫大B细胞淋巴瘤的研究进展[J]. 中国癌症杂志, 2022,32(3):258-267. DOI： 10.19401/j.cnki.1007-3639.2022.03.009.

Guangliang CHEN, Fangtian WU, Junning CAO. Advances in research on EBV positive diffuse large B-cell lymphoma, not otherwise specified[J]. China Oncology, 2022, 32(3): 258-267. DOI： 10.19401/j.cnki.1007-3639.2022.03.009.

摘要

EB病毒（Epstein-Barr virus

EBV）感染人体

后

可长期潜伏于静息记忆性或幼稚B淋巴细胞中。随着免疫系统的衰老

EBV感染者发生EBV相关恶性肿瘤的风险明显增加。非特指EBV阳性弥漫大B细胞淋巴瘤（EBV positive diffuse large B-cell lymphoma

not otherwise specified

EBV

DLBCL-NOS）是指发生在无已知免疫缺陷疾病或淋巴瘤病史

且肿瘤细胞核表达EBV编码RNA（EBV encoded RNA

EBER）的大B细胞淋巴瘤。流行病学研究显示

EBV

DLBCL-NOS主要流行于亚洲及拉丁美洲

多数患者年龄超过50岁。临床上

与EBV阴性DLBCL（EBV negative DLBCL

EBV

DLBCL）患者相比

EBV

DLBCL-NOS患者的临床病程更具侵袭性

初诊患者的临床分期多为晚期

且结外受累率可超过80%。老年患者通常较年轻患者的预后更差。尽管包括利妥昔单抗的免疫化疗方案可显著提高EBV

DLBCL患者的预后

EBV

DLBCL-NOS的最佳一线治疗方案仍需进一步探索。由于EBV

DLBCL-NOS的发病率相对较低并存在地区分布的差异

也缺乏多中心、高质量的前瞻性临床研究

因此临床医师对该特殊亚型淋巴瘤的认知仍比较有限。随着二代测序等新技术的开展

发现EBV

DLBCL-NOS的肿瘤细胞存在核因子-

#x003ba;B（nuclear factor-

#x003ba;B

NF-

#x003ba;B）和Janus激酶/信号转导和转录激活因子（Janus kinase/signal transducer and activator of transcription

JAK/STAT）等信号转导通路的改变

以及免疫过程如干扰素应答、抗原递呈系统和免疫检查点分子的异常等。这些基础研究成果促进了对相关治疗靶点的识别

有助于新治疗策略的探索。未来

嵌合抗原受体T细胞（chimeric antigen receptor T-cell

CAR-T）疗法、化疗联合免疫治疗及新型靶向治疗药物均有望改善EBV

DLBCL-NOS患者的预后

但仍需要更多研究证实。

Abstract

Epstein-Barr virus (EBV) can be latent in resting memory or naive B lymphocytes for a long time in affected people. Aging-induced immunosenescence is associated with an increased risk of EBV-related malignancies in EBV-infected patients. EBV positive diffuse large B-cell lymphoma

not otherwise specified (EBV

DLBCL-NOS) is identified as occurring in large B-cell lymphoma with no known history of immunodeficiency disease or lymphoma and whose tumor nuclei expressed EBV encoded RNA (EBER). The prevalence of EBV

DLBCL-NOS is significantly higher in Asia and Latin America than in other regions worldwide

and it mainly affects patients aged 50 years or older. EBV

DLBCL-NOS patients are associated with a more aggressive clinical course

a more advanced disease

and a higher rate of extra-nodal involvement (more than 80%) compared with EBV negative DLBCL (EBV

DLBCL) patients. The elderly patients

with EBV

DLBCL-NOS have poorer overall survival and progression-free survival than young adults. Rituximab-containing immunochemotherapy significantly improves the prognosis of patients with EBV

DLBCL

however

the optimal first-line treatment for EBV

DLBCL-NOS still needs to be further explored. The current understanding of EBV

DLBCL-NOS

a rare subtype of DLBCL

is very limited because of the relatively low incidence of EBV

DLBCL-NOS with a regional difference

as well as lacking high-quality clinical study. However

the DLBCL field is changing rapidly with new technologies

such as next-generation sequencing. To date

few studies have reported that multiple cells signaling pathways are aberrantly activated in tumor cells of EBV

DLBCL-NOS

such as nuclear factor-

#x003ba;B (NF-

#x003ba;B) and Janus kinase/signal transducer and activator of transcription (JAK/STAT). In addition

abnormalities in immune processes have been observed in tumor cells of EBV

DLBCL-NOS

such as the response to interferon

the antigen presentation system

and immune checkpoint molecules. The discovery of these basic research findings fosters the identification of relevant therapeutic targets and facilitates the exploration of novel therapeutic strategies. In the future

the benefits of immunotherapy

targeted therapy

and chimeric antigen receptor T-cell (CAR-T) therapy for EBV

DLBCL-NOS patients remain unknown and require extensive research.

关键词

Keywords

references

BELTRAN B E , CASTRO D , PAREDES S , et al . EBV-positive diffuse large B-cell lymphoma, not otherwise specified: 2020 update on diagnosis, risk-stratification and management [J ] . Am J Hematol , 2020 , 95 ( 4 ): 435 - 445 . DOI: 10.1002/ajh.v95.4 http://doi.org/10.1002/ajh.v95.4 https://onlinelibrary.wiley.com/toc/10968652/95/4 https://onlinelibrary.wiley.com/toc/10968652/95/4

SHANNON-LOWE C , RICKINSON A B , BELL A I . Epstein-Barr virus-associated lymphomas [J ] . Phil Trans R Soc B , 2017 , 372 ( 1732 ): 20160271 . DOI: 10.1098/rstb.2016.0271 http://doi.org/10.1098/rstb.2016.0271 https://royalsocietypublishing.org/doi/10.1098/rstb.2016.0271 https://royalsocietypublishing.org/doi/10.1098/rstb.2016.0271

FARRELL P J . Epstein-Barr virus and cancer [J ] . Annu Rev Pathol , 2019 , 14 : 29 - 53 . DOI: 10.1146/pathmechdis.2019.14.issue-1 http://doi.org/10.1146/pathmechdis.2019.14.issue-1 https://www.annualreviews.org/toc/pathmechdis/14/1 https://www.annualreviews.org/toc/pathmechdis/14/1

SMATTI M K , AL-SADEQ D W . ALI N H , et al . Epstein-Barr virus epidemiology, serology, and genetic variability of LMP-1 oncogene among healthy population: an update [J ] . Front Oncol , 2018 , 8 : 211 . DOI: 10.3389/fonc.2018.00211 http://doi.org/10.3389/fonc.2018.00211 https://www.frontiersin.org/article/10.3389/fonc.2018.00211/full https://www.frontiersin.org/article/10.3389/fonc.2018.00211/full

SAHA A , ROBERTSON E S . Mechanisms of B-cell oncogenesis induced by Epstein-Barr virus [J ] . J Virol , 2019 , 93 ( 13 ): e00238 - e00219 .

MARQUES-PIUBELLI M L , SALAS Y I , PACHAS C , et al . Epstein-Barr virus-associated B-cell lymphoproliferative disorders and lymphomas: a review [J ] . Pathology , 2020 , 52 ( 1 ): 40 - 52 . DOI: 10.1016/j.pathol.2019.09.006 http://doi.org/10.1016/j.pathol.2019.09.006 https://linkinghub.elsevier.com/retrieve/pii/S0031302519303964 https://linkinghub.elsevier.com/retrieve/pii/S0031302519303964

CHEN G L , XIA Z G , JIN J , et al . Characterization of artificial pneumothorax-unrelated pyothorax-associated lymphoma [J ] . J Oncol , 2021 , 2021 : 3869438 .

ARMITAGE J O . The changing classification of non-Hodgkin’s lymphomas [J ] . CA Cancer J Clin , 1997 , 47 ( 6 ): 323 - 325 . DOI: 10.3322/canjclin.47.6.323 http://doi.org/10.3322/canjclin.47.6.323 http://doi.wiley.com/10.3322/canjclin.47.6.323 http://doi.wiley.com/10.3322/canjclin.47.6.323

SCHMITZ R , WRIGHT G W , HUANG D W , et al . Genetics and pathogenesis of diffuse large B-cell lymphoma [J ] . N Engl J Med , 2018 , 378 ( 15 ): 1396 - 1407 . DOI: 10.1056/NEJMoa1801445 http://doi.org/10.1056/NEJMoa1801445 http://www.nejm.org/doi/10.1056/NEJMoa1801445 http://www.nejm.org/doi/10.1056/NEJMoa1801445

李小秋 , 李甘地 , 高子芬 , 等 . 中国淋巴瘤亚型分布: 国内多中心性病例10 002例分析 [J ] . 诊断学理论与实践 , 2012 , 11 ( 2 ): 111 - 115 .

LI X Q , LI G D , GAO Z F , et al . Distribution pattern of lymphoma subtypes in China: a nationwide multicenter study of 10 002 cases [J ] . J Diagn Concepts Pract , 2012 , 11 ( 2 ): 111 - 115 .

SUN J , YANG Q P , LU Z H , et al . Distribution of lymphoid neoplasms in China: analysis of 4 638 cases according to the World Health Organization classification [J ] . Am J Clin Pathol , 2012 , 138 ( 3 ): 429 - 434 . DOI: 10.1309/AJCP7YLTQPUSDQ5C http://doi.org/10.1309/AJCP7YLTQPUSDQ5C https://academic.oup.com/ajcp/article-lookup/doi/10.1309/AJCP7YLTQPUSDQ5C https://academic.oup.com/ajcp/article-lookup/doi/10.1309/AJCP7YLTQPUSDQ5C

HEALY J A , DAVE S S . The role of EBV in the pathogenesis of diffuse large B-cell lymphoma [J ] . Curr Top Microbiol Immunol , 2015 , 390 ( Pt 1 ): 315 - 337 .

OYAMA T , ICHIMURA K , SUZUKI R , et al . Senile EBV + B-cell lymphoproliferative disorders: a clinicopathologic study of 22 patients [J ] . Am J Surg Pathol , 2003 , 27 ( 1 ): 16 - 26 . DOI: 10.1097/00000478-200301000-00003 http://doi.org/10.1097/00000478-200301000-00003 http://journals.lww.com/00000478-200301000-00003 http://journals.lww.com/00000478-200301000-00003

OK C Y , PAPATHOMAS T G , MEDEIROS L J , et al . EBV-positive diffuse large B-cell lymphoma of the elderly [J ] . Blood , 2013 , 122 ( 3 ): 328 - 340 .

BELTRAN B E , MORALES D , QUIÑONES P , et al . EBV-positive diffuse large B-cell lymphoma in young immunocompetent individuals [J ] . Clin Lymphoma Myeloma Leuk , 2011 , 11 ( 6 ): 512 - 516 . DOI: 10.1016/j.clml.2011.07.003 http://doi.org/10.1016/j.clml.2011.07.003 https://linkinghub.elsevier.com/retrieve/pii/S2152265011002370 https://linkinghub.elsevier.com/retrieve/pii/S2152265011002370

HONG J Y , YOON D H , SUH C , et al . EBV-positive diffuse large B-cell lymphoma in young adults: is this a distinct disease entity? [J ] . Ann Oncol , 2015 , 26 ( 3 ): 548 - 555 . DOI: 10.1093/annonc/mdu556 http://doi.org/10.1093/annonc/mdu556 https://linkinghub.elsevier.com/retrieve/pii/S0923753419314164 https://linkinghub.elsevier.com/retrieve/pii/S0923753419314164

刘琳 , 高子芬 , 李敏 , 等 . EB病毒阳性的胃弥漫大B细胞淋巴瘤特点及预后 [J ] . 中国肿瘤临床 , 2016 , 43 ( 6 ): 255 - 259 .

LIU L , GAO Z F , LI M , et al . Characteristics and prognosis of EBV-positive gastric diffuse large B-cell lymphoma [J ] . Chin J Clin Oncol , 2016 , 43 ( 6 ): 255 - 259 .

SWERDLOW S H , CAMPO E , HARRIS N L , et al . WHO classification of tumours of haematopoietic and lymphoid tissues [M ] . WHO Classification of Tumours 4th Edition , 2017 : 2 .

LU T X , LIANG J H , MIAO Y , et al . Epstein-Barr virus positive diffuse large B-cell lymphoma predict poor outcome, regardless of the age [J ] . Sci Rep , 2015 , 5 : 12168 . DOI: 10.1038/srep12168 http://doi.org/10.1038/srep12168 https://doi.org/10.1038/srep12168 https://doi.org/10.1038/srep12168

PAN Y , MENG B , ZHANG H L , et al . Low incidence of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly in Tianjin, northern China [J ] . Leuk Lymphoma , 2013 , 54 ( 2 ): 298 - 303 . DOI: 10.3109/10428194.2012.715347 http://doi.org/10.3109/10428194.2012.715347 http://www.tandfonline.com/doi/full/10.3109/10428194.2012.715347 http://www.tandfonline.com/doi/full/10.3109/10428194.2012.715347

SONG C G , HUANG J J , LI Y J , et al . Epstein-Barr virus-positive diffuse large B-cell lymphoma in the elderly: a matched case-control analysis [J ] . PLoS One , 2015 , 10 ( 7 ): e0133973 . DOI: 10.1371/journal.pone.0133973 http://doi.org/10.1371/journal.pone.0133973 https://dx.plos.org/10.1371/journal.pone.0133973 https://dx.plos.org/10.1371/journal.pone.0133973

QIN C , HUANG Y , FENG Y , et al . Clinicopathological features and EBV infection status of lymphoma in children and adolescents in South China: a retrospective study of 662 cases [J ] . Diagn Pathol , 2018 , 13 ( 1 ): 17 . DOI: 10.1186/s13000-018-0693-0 http://doi.org/10.1186/s13000-018-0693-0 https://doi.org/10.1186/s13000-018-0693-0 https://doi.org/10.1186/s13000-018-0693-0

NAN F F , ZHANG L , LI L , et al . Clinical features and survival impact of EBV-positive diffuse large B-cell lymphoma with different age cutoffs [J ] . Eur Rev Med Pharmacol Sci , 2020 , 24 ( 17 ): 8947 - 8956 .

刘斌 . EBV阳性弥漫大B细胞淋巴瘤临床与分子生物学预后因素分析 [D ] . 海军军医大学 , 2018 .

LIU B . The clinical characteristics and molecular prognostic analysis of patients with EBV-positive diffuse large B-cell lymphoma [D ] . Naval Medical University , 2018 .

温晶晶 . EBV阳性弥漫大B细胞淋巴瘤的临床特征及二代组学研究 [D ] . 福建医科大学 , 2018 .

WEN J J . Analysis of clinical features and next generation sequencing of Epstein-Barr virus-positive diffuse large B-cell lymphoma [D ] . Fujian Medical University , 2018 .

GU Y Y , LUO B , LI C Y , et al . Expression and clinical significance of neuropilin-1 in Epstein-Barr virus-associated lymphomas [J ] . Cancer Biomark , 2019 , 25 ( 3 ): 259 - 273 . DOI: 10.3233/CBM-192437 http://doi.org/10.3233/CBM-192437 https://www.medra.org/servlet/aliasResolver?alias=iospress&amp;doi=10.3233/CBM-192437 https://www.medra.org/servlet/aliasResolver?alias=iospress&amp;doi=10.3233/CBM-192437

OK C Y , LI L , XU-MONETTE Z Y , et al . Prevalence and clinical implications of Epstein-Barr virus infection in de novo diffuse large B-cell lymphoma in Western countries [J ] . Clin Cancer Res , 2014 , 20 ( 9 ): 2338 - 2349 . DOI: 10.1158/1078-0432.CCR-13-3157 http://doi.org/10.1158/1078-0432.CCR-13-3157 http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-13-3157 http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-13-3157

胡晓梅 , 邱宗建 , 杨映红 . EBV阳性弥漫大B细胞淋巴瘤18例临床病理分析 [J ] . 临床与实验病理学杂志 , 2019 , 35 ( 8 ): 953 - 956 .

HU X M , QIU Z J , YANG Y H . Clinical and pathological analysis of 18 cases of EBV-positive diffuse large B-cell lymphoma [J ] . Chin J Clin Exp Pathol , 2019 , 35 ( 8 ): 953 - 956 .

GAO X J , LI J , WANG Y Q , et al . Clinical characteristics and prognostic significance of EBER positivity in diffuse large B-cell lymphoma: a meta-analysis [J ] . PLoS One , 2018 , 13 ( 6 ): e0199398 . DOI: 10.1371/journal.pone.0199398 http://doi.org/10.1371/journal.pone.0199398 https://dx.plos.org/10.1371/journal.pone.0199398 https://dx.plos.org/10.1371/journal.pone.0199398

OKAMOTO A , YANADA M , MIURA H , et al . Prognostic significance of Epstein-Barr virus DNA detection in pretreatment serum in diffuse large B-cell lymphoma [J ] . Cancer Sci , 2015 , 106 ( 11 ): 1576 - 1581 . DOI: 10.1111/cas.2015.106.issue-11 http://doi.org/10.1111/cas.2015.106.issue-11 https://onlinelibrary.wiley.com/toc/13497006/106/11 https://onlinelibrary.wiley.com/toc/13497006/106/11

NICOLAE A , PITTALUGA S , ABDULLAH S , et al . EBV-positive large B-cell lymphomas in young patients: a nodal lymphoma with evidence for a tolerogenic immune environment [J ] . Blood , 2015 , 126 ( 7 ): 863 - 872 .

OYAMA T , YAMAMOTO K , ASANO N , et al . Age-related EBV-associated B-cell lymphoproliferative disorders constitute a distinct clinicopathologic group: a study of 96 patients [J ] . Clin Cancer Res , 2007 , 13 ( 17 ): 5124 - 5132 . DOI: 10.1158/1078-0432.CCR-06-2823 http://doi.org/10.1158/1078-0432.CCR-06-2823 http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-06-2823 http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-06-2823

钟敏 , 苏群豪 , 徐璐 . 利妥昔单抗治疗EBV阳性弥漫性大B细胞性淋巴瘤患者疗效的影响因素分析 [J ] . 中国实验血液学杂志 , 2020 , 28 ( 4 ): 1210 - 1214 .

ZHONG M , SU Q H , XU L . Analysis of factors influencing clinical efficacy of rituximab on patients with Epstein-Barr virus positive diffuse large B-cell lymphoma [J ] . J Exp Hematol , 2020 , 28 ( 4 ): 1210 - 1214 .

BELTRAN B E , CASTILLO J J , MORALES D , et al . EBV-positive diffuse large B-cell lymphoma of the elderly: a case series from Peru [J ] . Am J Hematol , 2011 , 86 ( 8 ): 663 - 667 . DOI: 10.1002/ajh.v86.8 http://doi.org/10.1002/ajh.v86.8 http://doi.wiley.com/10.1002/ajh.v86.8 http://doi.wiley.com/10.1002/ajh.v86.8

LIU Z , XU-MONETTE Z Y , CAO X , et al . Prognostic and biological significance of survivin expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy [J ] . Mod Pathol , 2015 , 28 ( 10 ): 1297 - 1314 . DOI: 10.1038/modpathol.2015.94 http://doi.org/10.1038/modpathol.2015.94 https://doi.org/10.1038/modpathol.2015.94 https://doi.org/10.1038/modpathol.2015.94

JIANG X N , YU B H , YAN W H , et al . Epstein-Barr virus-positive diffuse large B-cell lymphoma features disrupted antigen capture/presentation and hijacked T-cell suppression [J ] . Oncoimmunology , 2019 , 9 ( 1 ): 1683346 . DOI: 10.1080/2162402X.2019.1683346 http://doi.org/10.1080/2162402X.2019.1683346 https://www.tandfonline.com/doi/full/10.1080/2162402X.2019.1683346 https://www.tandfonline.com/doi/full/10.1080/2162402X.2019.1683346

DOJCINOV S D , VENKATARAMAN G , PITTALUGA S , et al . Age-related EBV-associated lymphoproliferative disorders in the Western population: a spectrum of reactive lymphoid hyperplasia and lymphoma [J ] . Blood , 2011 , 117 ( 18 ): 4726 - 4735 . DOI: 10.1182/blood-2010-12-323238 http://doi.org/10.1182/blood-2010-12-323238 https://ashpublications.org/blood/article/117/18/4726/21375/Agerelated-EBVassociated-lymphoproliferative https://ashpublications.org/blood/article/117/18/4726/21375/Agerelated-EBVassociated-lymphoproliferative

HWANG J , SUH C H , WON KIM K , et al . The incidence of Epstein-Barr virus-positive diffuse large B-cell lymphoma: a systematic review and meta-analysis [J ] . Cancers , 2021 , 13 ( 8 ): 1785 . DOI: 10.3390/cancers13081785 http://doi.org/10.3390/cancers13081785 https://www.mdpi.com/2072-6694/13/8/1785 https://www.mdpi.com/2072-6694/13/8/1785

桂琳 , 何小慧 , 刘鹏 , 等 . 九例人免疫缺陷病毒阴性的浆母细胞淋巴瘤临床特征及文献复习 [J ] . 中华血液学杂志 , 2016 . 37 ( 9 ): 762 - 767 .

GUI L , HE X H , LIU P , et al . Clinical features and outcomes: analysis of 9 cases of HIV-negfive plasmablastic lymphoma [J ] . Chin J Hematol , 2016 . 37 ( 9 ): 762 - 767 .

LOPEZ A , ABRISQUETA P . Plasmablastic lymphoma: current perspectives [J ] . Blood Lymphat Cancer , 2018 , 8 : 63 - 70 .

YOON H , PARK S , JU H , et al . Integrated copy number and gene expression profiling analysis of Epstein-Barr virus-positive diffuse large B-cell lymphoma [J ] . Genes Chromosomes Cancer , 2015 , 54 ( 6 ): 383 - 396 . DOI: 10.1002/gcc.v54.6 http://doi.org/10.1002/gcc.v54.6 https://onlinelibrary.wiley.com/toc/10982264/54/6 https://onlinelibrary.wiley.com/toc/10982264/54/6

CHEN J G , KENDRICK S , QIN Z Q . Mechanistic insights into chemoresistance mediated by oncogenic viruses in lymphomas [J ] . Viruses , 2019 , 11 ( 12 ): 1161 . DOI: 10.3390/v11121161 http://doi.org/10.3390/v11121161 https://www.mdpi.com/1999-4915/11/12/1161 https://www.mdpi.com/1999-4915/11/12/1161

LUO Y , LIU Y T , WANG C K , et al . Signaling pathways of EBV-induced oncogenesis [J ] . Cancer Cell Int , 2021 , 21 ( 1 ): 93 . DOI: 10.1186/s12935-021-01793-3 http://doi.org/10.1186/s12935-021-01793-3 https://doi.org/10.1186/s12935-021-01793-3 https://doi.org/10.1186/s12935-021-01793-3

FISH K , COMOGLIO F , SHAFFER A L , et al . Rewiring of B-cell receptor signaling by Epstein-Barr virus LMP2A [J ] . PNAS , 2020 , 117 ( 42 ): 26318 - 26327 . DOI: 10.1073/pnas.2007946117 http://doi.org/10.1073/pnas.2007946117 https://pnas.org/doi/full/10.1073/pnas.2007946117 https://pnas.org/doi/full/10.1073/pnas.2007946117

KATO H , KARUBE K , YAMAMOTO K , et al . Gene expression profiling of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly reveals alterations of characteristic oncogenetic pathways [J ] . Cancer Sci , 2014 , 105 ( 5 ): 537 - 544 . DOI: 10.1111/cas.2014.105.issue-5 http://doi.org/10.1111/cas.2014.105.issue-5 https://onlinelibrary.wiley.com/toc/13497006/105/5 https://onlinelibrary.wiley.com/toc/13497006/105/5

INCROCCI R , BARSE L , STONE A , et al . Epstein-Barr virus latent membrane protein 2A (LMP2A) enhances IL-10 production through the activation of Bruton’s tyrosine kinase and STAT3 [J ] . Virology , 2017 , 500 : 96 - 102 . DOI: 10.1016/j.virol.2016.10.015 http://doi.org/10.1016/j.virol.2016.10.015 https://linkinghub.elsevier.com/retrieve/pii/S0042682216303142 https://linkinghub.elsevier.com/retrieve/pii/S0042682216303142

LIU F , WANG Z , ZHOU X G , et al . Genetic heterogeneity and mutational signature in Chinese Epstein-Barr virus-positive diffuse large B-cell lymphoma [J ] . PLoS One , 2018 , 13 ( 8 ): e0201546 . DOI: 10.1371/journal.pone.0201546 http://doi.org/10.1371/journal.pone.0201546 https://dx.plos.org/10.1371/journal.pone.0201546 https://dx.plos.org/10.1371/journal.pone.0201546

ZHOU Y Y , XU Z J , LIN W , et al . Comprehensive genomic profiling of EBV-positive diffuse large B-cell lymphoma and the expression and clinicopathological correlations of some related genes [J ] . Front Oncol , 2019 , 9 : 683 . DOI: 10.3389/fonc.2019.00683 http://doi.org/10.3389/fonc.2019.00683 https://www.frontiersin.org/article/10.3389/fonc.2019.00683/full https://www.frontiersin.org/article/10.3389/fonc.2019.00683/full

GEBAUER N , KÜNSTNER A , KETZER J , et al . Genomic insights into the pathogenesis of Epstein-Barr virus-associated diffuse large B-cell lymphoma by whole-genome and targeted amplicon sequencing [J ] . Blood Cancer J , 2021 , 11 ( 5 ): 102 . DOI: 10.1038/s41408-021-00493-5 http://doi.org/10.1038/s41408-021-00493-5 https://doi.org/10.1038/s41408-021-00493-5 https://doi.org/10.1038/s41408-021-00493-5

WU L , EHLIN-HENRIKSSON B , ZHOU X Y , et al . Epstein-Barr virus (EBV) provides survival factors to EBV + diffuse large B-cell lymphoma (DLBCL) lines and modulates cytokine induced specific chemotaxis in EBV + DLBCL [J ] . Immunology , 2017 , 152 ( 4 ): 562 - 573 . DOI: 10.1111/imm.2017.152.issue-4 http://doi.org/10.1111/imm.2017.152.issue-4 http://doi.wiley.com/10.1111/imm.2017.152.issue-4 http://doi.wiley.com/10.1111/imm.2017.152.issue-4

ZHANG B C , KRACKER S , YASUDA T , et al . Immune surveillance and therapy of lymphomas driven by Epstein-Barr virus protein LMP1 in a mouse model [J ] . Cell , 2012 , 148 ( 4 ): 739 - 751 . DOI: 10.1016/j.cell.2011.12.031 http://doi.org/10.1016/j.cell.2011.12.031 https://linkinghub.elsevier.com/retrieve/pii/S0092867412000992 https://linkinghub.elsevier.com/retrieve/pii/S0092867412000992

GUO L , BODO J , DURKIN L , et al . Evaluation of PD1/PD-L1 expression and their clinicopathologic association in EBV-associated lymphoproliferative disorders in nonimmunosuppressed patients [J ] . Appl Immunohistochem Mol Morphol , 2019 , 27 ( 2 ): 101 - 106 . DOI: 10.1097/PAI.0000000000000583 http://doi.org/10.1097/PAI.0000000000000583 https://journals.lww.com/00129039-201902000-00003 https://journals.lww.com/00129039-201902000-00003

YOON S E , KIM S J , YOON D H , et al . A phase Ⅱ study of ibrutinib in combination with rituximab-cyclophosphamide-doxorubicin hydrochloride-vincristine sulfate-prednisone therapy in Epstein-Barr virus-positive, diffuse large B-cell lymphoma (54179060LYM2003: IVORY study): results of the final analysis [J ] . Ann Hematol , 2020 , 99 ( 6 ): 1283 - 1291 . DOI: 10.1007/s00277-020-04005-6 http://doi.org/10.1007/s00277-020-04005-6 https://doi.org/10.1007/s00277-020-04005-6 https://doi.org/10.1007/s00277-020-04005-6

PERRINE S P , HERMINE O , SMALL T , et al . A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies [J ] . Blood , 2007 , 109 ( 6 ): 2571 - 2578 . DOI: 10.1182/blood-2006-01-024703 http://doi.org/10.1182/blood-2006-01-024703 https://ashpublications.org/blood/article/109/6/2571/23296/A-phase-12-trial-of-arginine-butyrate-and https://ashpublications.org/blood/article/109/6/2571/23296/A-phase-12-trial-of-arginine-butyrate-and

GHOSH S K , PERRINE S P , WILLIAMS R M , et al . Histone deacetylase inhibitors are potent inducers of gene expression in latent EBV and sensitize lymphoma cells to nucleoside antiviral agents [J ] . Blood , 2012 , 119 ( 4 ): 1008 - 1017 . DOI: 10.1182/blood-2011-06-362434 http://doi.org/10.1182/blood-2011-06-362434 https://ashpublications.org/blood/article/119/4/1008/29689/Histone-deacetylase-inhibitors-are-potent-inducers https://ashpublications.org/blood/article/119/4/1008/29689/Histone-deacetylase-inhibitors-are-potent-inducers

SHIN D Y , KIM A , KANG H J , et al . Histone deacetylase inhibitor romidepsin induces efficient tumor cell lysis via selective down-regulation of LMP1 and c-MYC expression in EBV - positive diffuse large B-cell lymphoma [J ] . Cancer Lett , 2015 , 364 ( 2 ): 89 - 97 . DOI: 10.1016/j.canlet.2015.03.016 http://doi.org/10.1016/j.canlet.2015.03.016 https://linkinghub.elsevier.com/retrieve/pii/S0304383515001962 https://linkinghub.elsevier.com/retrieve/pii/S0304383515001962

PORCU P , HAVERKOS B , ALPDOGAN O , et al . Oral nanatinostat (nstat) and valganciclovir (VGCV) in patients with recurrent Epstein-Barr virus (EBV)-positive lymphomas: initial phase 2 results [J ] . Blood , 2020 , 136 ( Supplement 1 ): 7 - 8 .

RAMOS J C , SPARANO J A , RUDEK M A , et al . Safety and preliminary efficacy of vorinostat with R-EPOCH in high-risk HIV-associated non-Hodgkin's lymphoma (AMC-075) [J ] . Clin Lymphoma Myeloma Leuk , 2018 , 18(3): 180-190.e2.

CHEN B J , CHAPUY B , OUYANG J , et al . PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies [J ] . Clin Cancer Res , 2013 , 19 ( 13 ): 3462 - 3473 . DOI: 10.1158/1078-0432.CCR-13-0855 http://doi.org/10.1158/1078-0432.CCR-13-0855 http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-13-0855 http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-13-0855

KIYASU J , MIYOSHI H , HIRATA A , et al . Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma [J ] . Blood , 2015 , 126 ( 19 ): 2193 - 2201 .

GREEN M R , RODIG S , JUSZCZYNSKI P , et al . Constitutive AP-1 activity and EBV infection induce PD-L1 in Hodgkin lymphomas and posttransplant lymphoproliferative disorders: implications for targeted therapy [J ] . Clin Cancer Res , 2012 , 18 ( 6 ): 1611 - 1618 . DOI: 10.1158/1078-0432.CCR-11-1942 http://doi.org/10.1158/1078-0432.CCR-11-1942 http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-11-1942 http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-11-1942

ANSELL S M , MINNEMA M C , JOHNSON P , et al . Nivolumab for relapsed/refractory diffuse large B-cell lymphoma in patients ineligible for or having failed autologous transplantation: a single-arm, phase Ⅱ study [J ] . J Clin Oncol , 2019 , 37 ( 6 ): 481 - 489 .

SMITH S D , TILL B G , SHADMAN M S , et al . Pembrolizumab with R-CHOP in previously untreated diffuse large B-cell lymphoma: potential for biomarker driven therapy [J ] . Br J Haematol , 2020 , 189 ( 6 ): 1119 - 1126 . DOI: 10.1111/bjh.v189.6 http://doi.org/10.1111/bjh.v189.6 https://onlinelibrary.wiley.com/toc/13652141/189/6 https://onlinelibrary.wiley.com/toc/13652141/189/6

YOUNES A , BURKE J M , CHESON B , et al . Safety and efficacy of atezolizumab in combination with rituximab plus CHOP in previously untreated patients with diffuse large B-cell lymphoma (DLBCL): primary analysis of a phase Ⅰ/Ⅱ study [J ] . Blood , 2018 , 132 : 2969 . DOI: 10.1182/blood-2018-99-116678 http://doi.org/10.1182/blood-2018-99-116678 https://ashpublications.org/blood/article/132/Supplement%201/2969/263470/Safety-and-Efficacy-of-Atezolizumab-in-Combination https://ashpublications.org/blood/article/132/Supplement%201/2969/263470/Safety-and-Efficacy-of-Atezolizumab-in-Combination

TANG X J , ZHOU Y , LI W J , et al . T cells expressing a LMP1-specific chimeric antigen receptor mediate antitumor effects against LMP1-positive nasopharyngeal carcinoma cells in vitro and in vivo [J ] . J Biomed Res , 2014 , 28 ( 6 ): 468 - 475 .

BOLLARD C M , GOTTSCHALK S , TORRANO V , et al . Sustained complete responses in patients with lymphoma receiving autologous cytotoxic T lymphocytes targeting Epstein-Barr virus latent membrane proteins [J ] . J Clin Oncol , 2014 , 32 ( 8 ): 798 - 808 . DOI: 10.1200/JCO.2013.51.5304 http://doi.org/10.1200/JCO.2013.51.5304 http://ascopubs.org/doi/10.1200/JCO.2013.51.5304 http://ascopubs.org/doi/10.1200/JCO.2013.51.5304

ZOU P , KAWADA J , PESNICAK L , et al . Bortezomib induces apoptosis of Epstein-Barr virus (EBV)-transformed B-cells and prolongs survival of mice inoculated with EBV - transformed B-cells [J ] . J Virol , 2007 , 81 ( 18 ): 10029 - 10036 . DOI: 10.1128/JVI.02241-06 http://doi.org/10.1128/JVI.02241-06 https://journals.asm.org/doi/10.1128/JVI.02241-06 https://journals.asm.org/doi/10.1128/JVI.02241-06

RUAN J , MARTIN P , FURMAN R R , et al . Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma [J ] . J Clin Oncol , 2011 , 29 ( 6 ): 690 - 697 . DOI: 10.1200/JCO.2010.31.1142 http://doi.org/10.1200/JCO.2010.31.1142 http://ascopubs.org/doi/10.1200/JCO.2010.31.1142 http://ascopubs.org/doi/10.1200/JCO.2010.31.1142

OFFNER F , SAMOILOVA O , OSMANOV E , et al . Frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL [J ] . Blood , 2015 , 126 ( 16 ): 1893 - 1901 .

SANG A X , MCPHERSON M C , IVISON G T , et al . Dual blockade of the PI3K/AKT/mTOR pathway inhibits posttransplant Epstein-Barr virus B-cell lymphomas and promotes allograft survival [J ] . Am J Transplant , 2019 , 19 ( 5 ): 1305 - 1314 . DOI: 10.1111/ajt.2019.19.issue-5 http://doi.org/10.1111/ajt.2019.19.issue-5 https://onlinelibrary.wiley.com/toc/16006143/19/5 https://onlinelibrary.wiley.com/toc/16006143/19/5

WANG Q , ZHU N N , HU J Y , et al . The mTOR inhibitor manassantin B reveals a crucial role of mTORC2 signaling in Epstein-Barr virus reactivation [J ] . J Biol Chem , 2020 , 295 ( 21 ): 7431 - 7441 . DOI: 10.1074/jbc.RA120.012645 http://doi.org/10.1074/jbc.RA120.012645 https://linkinghub.elsevier.com/retrieve/pii/S0021925817502744 https://linkinghub.elsevier.com/retrieve/pii/S0021925817502744

浏览量

4651

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

靶向治疗及免疫治疗联合化疗为产AFP阳性结肠癌患者带来显著获益1例病例报告并文献复习

转移性结直肠癌三线治疗的研究现状及进展

卡瑞利珠单抗联合化疗及靶向治疗在复发、转移及初治晚期宫颈癌中的疗效与安全性分析：一项回顾性队列研究

恶性胸膜间皮瘤治疗的研究现状与展望

靶向治疗与免疫治疗在放射性碘难治性分化型甲状腺癌中的应用与前景