胡俊霞, 陈清江, 张旭东, 李文才, 王冠男, 王欣, 董萌, 吴少璇, 马咪静, 尹美凤, 杨万秋, 丁梦杰, 张明智, 朱利楠. PD-1/PD-Ls在EBV阳性T/NK淋巴组织增殖性疾病中的表达及临床意义[J]. 中国肿瘤临床, 2018, 45(24): 1248-1253. DOI: 10.3969/j.issn.1000-8179.2018.24.174
引用本文: 胡俊霞, 陈清江, 张旭东, 李文才, 王冠男, 王欣, 董萌, 吴少璇, 马咪静, 尹美凤, 杨万秋, 丁梦杰, 张明智, 朱利楠. PD-1/PD-Ls在EBV阳性T/NK淋巴组织增殖性疾病中的表达及临床意义[J]. 中国肿瘤临床, 2018, 45(24): 1248-1253. DOI: 10.3969/j.issn.1000-8179.2018.24.174
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Hu Junxia, Chen Qingjiang, Zhang Xudong, Li Wencai, Wang Guannan, Wang Xin, Dong Meng, Wu Shaoxuan, Ma Mijing, Yin Meifeng, Yang Wanqiu, Ding, Zhang Mingzhi, Zhu Linan. Expression and clinical significance of PD-1/PD-Ls in EBV-positive T/NK lymphoproliferative disorders[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2018, 45(24): 1248-1253. DOI: 10.3969/j.issn.1000-8179.2018.24.174
Citation: Hu Junxia, Chen Qingjiang, Zhang Xudong, Li Wencai, Wang Guannan, Wang Xin, Dong Meng, Wu Shaoxuan, Ma Mijing, Yin Meifeng, Yang Wanqiu, Ding, Zhang Mingzhi, Zhu Linan. Expression and clinical significance of PD-1/PD-Ls in EBV-positive T/NK lymphoproliferative disorders[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2018, 45(24): 1248-1253. DOI: 10.3969/j.issn.1000-8179.2018.24.174
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PD-1/PD-Ls在EBV阳性T/NK淋巴组织增殖性疾病中的表达及临床意义

Expression and clinical significance of PD-1/PD-Ls in EBV-positive T/NK lymphoproliferative disorders

    摘要
  • 摘要:
      目的  探讨程序性细胞死亡蛋白-1（programmed cell death protein 1，PD-1）、程序性细胞死亡蛋白-2配体（programmed death-ligand 2，PD-L2）及程序性细胞死亡蛋白-1配体（programmed death-ligand 1，PD-L1）在EB病毒（Epstein-Barr virus，EBV）阳性T/NK淋巴组织增殖性疾病Epstein-Barr virus-positive T/natural killer（NK）-cell lymphoproliferative disease，EBV（+）-T/NKLPD中的表达及临床意义。
      方法  收集2013年1月至2017年12月郑州大学第一附属医院17例EBV（+）-T/NK-LPD患者的病理石蜡包埋组织，其中男性12例，女性5例，年龄为10~82岁，平均年龄29岁，Ⅰ级4例，Ⅱ级7例，Ⅲ级3例，种痘水疱病样淋巴组织增殖性疾病3例。采用免疫组织化学SP法检测PD-1、PD-L1和PD-L2在人EBV（+）-T/NK-LPD组织中的表达，并采用Fisher确切概率法、Spearman秩相关，分析其与临床病理学参数、病理分级及患者预后之间的关系。
      结果  在17例组织标本中，PD-1表达阳性12例，PD-L1表达阳性6例，PD-L2表达阳性5例。PD-1、PD-L2的表达与预后无显著相关性（P>0.05），PD-L1的表达与预后呈正相关（P < 0.05）。PD-L1、PD-L2的表达与年龄、性别、LDH水平及Ki-67表达水平之间无显著相关性（P>0.05）。PD-1及PDL2的表达与病理分级之间无显著相关性（r=0.141，r=-0.149，均P>0.05），而PD-L1的表达与病理分级之间呈负相关（r=-0.563），PD-L1的表达与病理分级之间的相关关系具有统计学意义（P < 0.05）。
      结论  PD-1、PD-L1和PD-L2在EBV（+）-T/NK-LPD病理组织中异常表达，虽然PD-1的表达与预后、病理分级之间无显著相关性，但在EBV（+）T/NK-LPD中显著高表达，PD-1/PD-Ls信号通路可能成为EBV（+）-T/NK-LPD免疫治疗的潜在新靶点。

     

    Abstract:
      Objective  To investigate the expression and clinical significance of programmed death-ligand 1 (PD-L1), programmed death-ligand 2 (PD-L2), and their receptor programmed cell death protein 1 (PD-1) in EBV-positive T/NK lymphoproliferative disease Epstein-Barr viruspositive T/natural killer (NK)-cell lymphoproliferative disease, EBV(+)-T/NK-LPD.
      Methods  The pathological paraffin-embedded tissues of 17 patients with EBV(+)-T/NK-LPD from the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2017 were collected. These patients include 12 males and 5 females, aged 10-82 years old, the average age being 29 years, 4 people in grade Ⅰ, 7 in grade Ⅱ, 3 in grade Ⅲ, and 3 people with hydroa vacciniforme-like lymphoproliferative disorders. Immunohistochemical SP method was used to detect the expression of PD-1, PD-L1, and PD-L2 in human EBV(+)-T/NK-LPD tissues. The relationship between PD-1, PD-L1, PD-L2 expression, and clinicopathological parameters, pathological grades and prognosis were analyzed by Fisher's exact probabilities and Spearman rank correlation.
      Result  After statistical analysis, the results showed that in 17 cases of tissue samples, there were 12 cases with positive PD-1 expression, 6 cases with positive PD-L1 expression and 5 cases with positive PD-L2 expression. There was no significant correlation between PD-1 and PD-L2 expression and prognosis (P>0.05). PD-L1 expression showed a positive correlation with prognosis (P < 0.05). There was no significant correlation between the expression of PD-L1 and PD-L2 with age, sex, as well as LDH and Ki-67 levels (P>0.05). Moreover, there was no significant correlation of PD-1 and PD-L2 expression with pathological grade (r=0.141, r=-0.149, both P>0.05). However, there was a negative correlation between the PD-L1 expression and pathological grade (r=-0.563), and the correlation between the PD-L1 expression and pathological grade was statistically significant (P < 0.05).
      Conclusions  PD-1, PD-L1, and PD-L2 are abnormally expressed in the pathological tissues of EBV(+)-T/NK-LPD. Although there was no significant correlation between the expression of PD-1 and prognosis or pathological grade, it was significantly higher in EBV+T/NK-LPD. PD-1/PD-Ls associated signaling pathway is expected to be a potential new target for EBV(+)-T/NK-LPD immunotherapy.

     

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