儿童异基因造血干细胞移植后淋巴组织增殖性疾病程序性死亡受体-1和程序性死亡配体-1的表达  

Expression of programmed death-1 and programmed death-ligand 1 in post-transplant lymphoproliferative disorders after allogeneic hematopoietic stem cell transplantation in children

作　　者：曹娟[1] 文飞球[1] 杨国城 张欢[1] 何潇潇[1] 王春静[2] 缪秋玲[1] 陈永先 何鹏 刘四喜[2] Cao Juan;Wen Feiqiu;Yang Guocheng;Zhang Huan;He Xiaoxiao;Wang Chunjing;Miao Qiuling;Chen Yong-xian;He Peng;Liu Sixi(Department of Pathology,Shenzhen Children′s Hospital,Shenzhen 518038,Guangdong Province,China;Department of Hematology-Oncology,Shenzhen Children′s Hospital,Shenzhen 518038,Guangdong Province,China)

机构地区：[1]深圳市儿童医院病理科,广东深圳518038 [2]深圳市儿童医院血液肿瘤科,广东深圳518038

出　　处：《中华实用儿科临床杂志》2021年第15期1161-1165,共5页Chinese Journal of Applied Clinical Pediatrics

基　　金：深圳小儿血液肿瘤分子医学公共服务平台。

摘　　要：目的探讨儿童异基因造血干细胞移植(allo-HSCT)后淋巴组织增殖性疾病(PTLD)中程序性死亡受体-1(PD-1)及程序性死亡配体-1(PD-L1)的表达及临床病理特征,明确PD-1/PD-L1抑制剂的检查点抑制是否可以作为一种治疗选择。方法回顾性分析2012年1月1日至2019年12月30日深圳市儿童医院13例病理确诊的allo-HSCT后PTLD的临床资料,采用免疫组织化学MaxVision™法染色、EB病毒(EBV)原位杂交及淋巴瘤基因重排检测,分析PD-1及PD-L1的表达与PTLD临床病理特征的关系。结果肿瘤细胞PD-1表达与患儿性别、年龄、基础疾病、组织学类型、移植方式及EBV原位杂交表达无关(均P>0.05)。而PD-L1的表达与组织学类型有关(P<0.05),其中PD-L1阳性率重型β-珠蛋白生成障碍性贫血(90.0%,9/10例)高于重型再生障碍性贫血(66.7%,2/3例),单形性PTLD(100.0%,2/2例)高于多形性PTLD(83.3%,5/6例),EBV阳性PTLD(90.9%,10/11例)高于EBV阴性PTLD(50.0%,1/2例)。13例PTLD中PD-1及PD-L1在肿瘤细胞中的阳性率分别为46.2%(6/13例)和61.5%(8/13例),在微环境细胞中的阳性率分别为92.3%(12/13例)和76.9%(10/13例),EBV阳性率为84.6%(11/13例)。结论PD-L1在单形性PTLD的肿瘤细胞中有更高的阳性率;且在标准免疫治疗和化疗无效的情况下,可对所有类型的PTLD进行PD-1和PD-L1的常规染色。Objective To explore the expressions of programmed death-1(PD-1)and programmed death-ligand 1(PD-L1)and clinicopathological characteristics in post-transplant lymphoproliferative disorder(PTLD)after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in children,with the aim of clarifying whether checkpoint inhibition of PD-1/PD-L1 inhibitors may serve as a therapy option.Methods The clinical data of 13 cases of PTLD after allo-HSCT pathologically confirmed in Shenzhen Children′s Hospital from January 1,2012 to December 30,2019 were retrospectively analyzed.The detection was performed by immunohistochemical staining by MaxVision™method,Epstein-Barr virus(EBV)in situ hybridization and lymphoma gene rearrangement.The relationship between the expression of PD-1 and PD-L1 and the clinicopathological characteristics of PTLD were analyzed.Results The expression of PD-1 was not correlated with gender,age,primary diseases,histopathological types,transplantation mode and the expression of EBV in situ hybridization(all P>0.05).The expression of PD-L1 was correlated with histopathological types(P<0.05).Furthermore,the expression rate of PD-L1 on severeβ-thalassemia was significantly higher than that of severe aplastic anemia[90.0%(9/10 cases)vs.66.7%(2/3 cases)]and monomorphic PTLD was higher than that of polymorphic PTLD[100.0%(2/2 cases)vs.83.3%(5/6 cases)].Moreover,the positive PTLD in EBV was higher than the negative PTLD in EBV[90.9%(10/11 cases)vs.50.0%(1/2 cases)].The positive rates of PD-1 and PD-L1 in 13 cases with PTLD were 46.2%(6/13 cases)and 61.5%(8/13 cases)in tumor cells,92.3%(12/13 cases)and 76.9%(10/13 cases)in microenvironmental cells,and 84.6%(11/13 cases)in EBV,respectively.Conclusions PD-L1 has a higher positive rate in tumor cells with monomorphic PTLD;and routine staining for PD-1 and PD-L1 can be performed in all types of PTLD when standard immunotherapy and chemotherapy are ineffective.

关 键 词：移植后淋巴组织增生性疾病 免疫检查点 程序性死亡受体-1 程序性死亡配体-1 

分 类 号：R551.2[医药卫生—血液循环系统疾病]