The expression and clinical relevance of PD-1, PD-L1, and TP63 in patients with diffuse large B-cell lymphoma.
The expression and clinical relevance of PD-1, PD-L1, and TP63 in patients with diffuse large B-cell lymphoma.
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弥漫性大 B 细胞淋巴瘤患者中 PD-1、PD-L1 和 TP63 的表达及其临床相关性。
DOI：
10.1097/md.0000000000006398
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发表时间：
2017-04
期刊：
影响因子：
1.6
通讯作者：
Zeng Y
中科院分区：
文献类型：
--
作者：
Fang X;Xiu B;Yang Z;Qiu W;Zhang L;Zhang S;Wu Y;Zhu X;Chen X;Xie S;Yi X;Liang A;Zeng Y
最新研究表明，在弥漫性大B细胞淋巴瘤（DLBCL）中可以发现程序性细胞死亡配体1（PD-L1）（分化簇274）和TP 63（肿瘤蛋白63）之间的新型易位，导致它们在RNA水平上在肿瘤细胞中的联合过表达。然而，这两种基因在DLBCL中蛋白水平的表达模式在很大程度上仍然未知，并且DLBCL中PD-L1和TP 63表达的临床相关性也不清楚。使用EnVision系统对来自76名中国DLBCL患者的肿瘤组织进行程序性细胞死亡1（PD-1）、PD-L1和TP 63的免疫染色。采用卡方检验、Kaplan-Meier曲线对数秩检验和考克斯比例风险回归模型分析PD-1、PD-L1和TP 63在74例DLBCL中的临床意义。PD-1主要表达于39.5%的肿瘤浸润淋巴细胞（TIL）。PD-L1在26.3%的患者肿瘤细胞中表达，TP 63在31.6%的患者肿瘤细胞核仁中表达。PD-1表达与患者性别、B症状相关（P = 0.032，P = 0.026）。 肿瘤细胞中PD-L1或TP 63表达的DLBCL显示出较低的国际预后指数（IPI）评分（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表达与患者的临床结局较差相关（P = 0.049）。 TP 63的免疫反应性与患者的生存时间无关。PD-1表达、患者年龄、安阿伯分期和IPI评分是OS的重要预后指标，而PD-L1和TP 63无预后意义。PD-1、PD-L1和TP 63在DLBCL中频繁表达。PD-1/PD-L1/TP 63阻断可能是某些患者的潜在治疗策略。
Supplemental Digital Content is available in the text 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.