[Correlation analysis of the Epstein-Barr virus recruited regulatory T cells in nasopharyngeal carcinoma of immune escape]

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2017 Sep 7;52(9):692-697. doi: 10.3760/cma.j.issn.1673-0860.2017.09.011.
[Article in Chinese]

Abstract

Objective: To investigate the relation of Epstein-Barr virus (EBV)-induced immune escape to regulatory T cells(Treg) in nasopharyngeal carcinoma(NPC). Methods: We recruited 83 patients who were pathologically diagnozed as nasopharyngeal carcinoma and treated in Nanfang Hospital from January to September 2016. CD4(+) CD25(+) FOXP3(+) Treg in peripheral blood was examined by flow cytometry and the level of EBV DNA in the blood was detected by quantitative real-time polymerase chain reaction(qRT-PCR)in 83 patients and 51 healthy adults as control. The expression of FOXP3(+) Treg and EBER in NPC in 32 of 83 patients and in nasopharyngitis in 16 control patients were tested by immunohistochemistry(IHC) and in-situ hybridization(ISH). Results: The ratio of Treg in blood in patients with NPC(5.29±1.45)% was higher than that in control group (4.78±1.19) %, with a statistically significant difference(P=0.035). The ratio of Treg in blood in patients with positive EBV was higher than that in patients with negative EBV(P=0.013), and there was a positive correlation between EBV DNA copies and Treg ratio(r=0.335, P=0.002). The density of FOXP3(+) Treg in NPC was higher than that in nasopharyngitis(P=0.001). Positive correlation was found between the density of FOXP3(+) Treg and the stain intensity of EBER(r=0.496, P=0.004). Conclusion: The ratios of Treg in blood and tissue in NPC patients with positive EBV are significantly increased, indicating a role of Treg in EBV-induced immune escape in NPC.

目的: 研究EB病毒感染阳性鼻咽癌与调节性T细胞(regulatory T cells, Treg)的相关性。 方法: 收集2016年1月至9月南方医科大学南方医院经病理确诊的初治鼻咽癌患者83例和健康成人对照51名,采集外周血,分别采用实时荧光聚合酶链(qRT-PCR)检测血清中EB病毒DNA含量和流式细胞术检测CD4(+) CD25(+) FOXP3(+) Treg细胞比例。83例患者中保留有鼻咽癌组织标本32例,另收集鼻咽炎组织16例为对照组,分别采用免疫组化法检测FOXP3(+) Treg的表达和原位杂交检测EBER的表达。 结果: 鼻咽癌外周血Treg细胞比例为(5.29±1.45)%,较对照组(4.78±1.19)%高,差异有统计学意义(P=0.035);EBV阳性组的Treg比例显著高于阴性组(P=0.013),且EBV DNA拷贝数与Treg细胞比例呈正相关(r=0.335,P=0.002);鼻咽癌组织的FOXP3(+) Treg细胞浸润密度为87.8个/高倍视野,显著高于炎症组织40.8个/高倍视野,差异有统计学意义(P=0.001);与EBER显色程度呈显著正相关(r=0.496,P=0.004)。 结论: EB病毒阳性鼻咽癌患者外周血及组织中Treg细胞比例显著增高,提示EB病毒可能通过募集Treg细胞参与鼻咽癌免疫逃逸。.

Keywords: Epstein-Barr virus; Immune escape; Nasopharyngeal neoplasms; T-lymphocytes, regulatory.

MeSH terms

  • Adult
  • Case-Control Studies
  • Forkhead Transcription Factors / blood
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Nasopharyngeal Carcinoma / immunology*
  • Nasopharyngeal Carcinoma / virology
  • Nasopharyngeal Neoplasms / immunology*
  • Nasopharyngeal Neoplasms / virology
  • T-Lymphocytes, Regulatory / immunology*
  • Tumor Escape / immunology*

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors