Fang Xia, Xiu Bing, Yang Zhizhang, Qiu Weizhe, Zhang Long, Zhang Suxia, Wu Yunjin, Zhu Xuyou, Chen Xue, Xie Suhong, Yi Xianghua, Liang Aibin, Zeng Yu
Department of Hematology Deparment of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN Department of Laboratory, Shanghai Zhongliu Hospital, Shanghai Fudan University School of Medicine, Shanghai, China.
Medicine (Baltimore). 2017 Apr;96(15):e6398. doi: 10.1097/MD.0000000000006398.
Latest study showed that a novel translocation between programmed cell death ligand 1 (PD-L1) (cluster of differentiation 274) and TP63 (tumor protein 63) can be found in diffuse large B-cell lymphoma (DLBCL), resulting in their conjunct overexpression in tumor cells at RNA level. However, the expressed pattern of these 2 genes at protein level in DLBCL remains largely unknown, and the clinical relevance of PD-L1 and TP63 expression in DLBCL are also unclear.Tumor tissues from 76 Chinese DLBCL patients were immunostained for programmed cell death 1 (PD-1), PD-L1, and TP63 using the EnVision system. Clinical relevance of PD-1, PD-L1, and TP63 in 74 DLBCL were analyzed by chi-square test, the Kaplan-Meier curves with log rank test, and Cox's proportional hazards regression model.PD-1 was mainly expressed in tumor-infiltrating lymphocytes (TILs) of 39.5% patients. PD-L1 was expressed in tumor cells of 26.3% patients, and TP63 was immunostained in nucleoli of tumor cells of 31.6% cases. PD-1 expression was significantly associated with the patients' gender and B symptoms (P = 0.032, P = 0.026). DLBCL with PD-L1 or TP63 expression in tumor cells showed low International Prognostic Index (IPI) score (P = 0.007, P = 0.009). PD-1 TILs was related to prolonged overall survival rate (OS) of DLBCL patients (P = 0.02), whereas PD-L1 expression was associated with worse clinical outcome of patients (P = 0.049). Immunoreactivity of TP63 was not correlated with patients' survival time. Besides, PD-1 expression, patients' age, Ann Arbor stage, and IPI score were significant prognostic markers for OS, but PD-L1 and TP63 had no prognostic significance.PD-1, PD-L1, and TP63 are frequently expressed in DLBCL. PD-1/PD-L1/TP63 blockade may be a potential therapeutic strategy for some patients.
最新研究表明，在弥漫性大B细胞淋巴瘤（DLBCL）中可发现程序性细胞死亡配体1（PD-L1，分化簇274）与TP63（肿瘤蛋白63）之间存在一种新的易位，导致它们在RNA水平上于肿瘤细胞中共同过表达。然而，这两个基因在DLBCL中蛋白质水平的表达模式仍基本未知，且PD-L1和TP63在DLBCL中的临床相关性也不清楚。使用EnVision系统对76例中国DLBCL患者的肿瘤组织进行程序性细胞死亡1（PD-1）、PD-L1和TP63免疫染色。通过卡方检验、对数秩检验的Kaplan-Meier曲线和Cox比例风险回归模型分析74例DLBCL中PD-1、PD-L1和TP63的临床相关性。PD-1主要在39.5%患者的肿瘤浸润淋巴细胞（TILs）中表达。PD-L1在26.3%患者的肿瘤细胞中表达，TP63在31.6%病例的肿瘤细胞核仁中免疫染色。PD-1表达与患者性别和B症状显著相关（P = 0.032，P = 0.026）。肿瘤细胞中表达PD-L1或TP63的DLBCL显示国际预后指数（IPI）评分较低（P = 0.007，P = 0.009）。PD-1 TILs与DLBCL患者的总生存率（OS）延长相关（P = 0.02），而PD-L1表达与患者较差的临床结局相关（P = 0.049）。TP63的免疫反应性与患者生存时间无关。此外，PD-1表达、患者年龄、Ann Arbor分期和IPI评分是OS的显著预后标志物，但PD-L1和TP63无预后意义。PD-1、PD-L1和TP63在DLBCL中经常表达。PD-1/PD-L1/TP63阻断可能是部分患者的一种潜在治疗策略。
