爱泼斯坦-巴尔病毒相关鼻咽癌中PD-L1和PD-1表达及CD8 +肿瘤浸润淋巴细胞的特征分析
Characterization of PD-L1 and PD-1 Expression and CD8+ Tumor-infiltrating Lymphocyte in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma.
作者信息
Larbcharoensub Noppadol, Mahaprom Komkrit, Jiarpinitnun Chuleeporn, Trachu Narumol, Tubthong Nattha, Pattaranutaporn Poompis, Sirachainan Ekaphop, Ngamphaiboon Nuttapong
机构信息
Department of Pathology.
Department of Medicine, Division of Medical Oncology.
出版信息
Am J Clin Oncol. 2018 Dec;41(12):1204-1210. doi: 10.1097/COC.0000000000000449.
OBJECTIVES
Immunotherapies that target the programmed death-1/ programmed death-1 ligand (PD-1/PD-L1) immune checkpoint pathway have shown promise in nasopharyngeal carcinoma (NPC) in early phases clinical studies. Here, we evaluated PD-1 and PD-L1 expression and CD8+ tumor-infiltrating lymphocytes (TILs) in NPC patients.
MATERIALS AND METHODS
Newly diagnosed NPC patients were identified through the institutional database between January 2007 and December 2012. PD-L1 and PD-1 expression, Epstein-Barr virus (EBV) status, and CD8+ TIL numbers were measured in archival tumor samples at diagnosis and their correlations with clinicopathologic features, including survival, were evaluated.
RESULTS
A total of 114 NPC patients were analyzed. Most patients (96%) were EBV positive. PD-L1 was expressed in ≥1% of tumor cells (TCs) in 69% of patients, in ≥50% of TCs in 12% of patients, and in ≥5% of either TCs or infiltrating immune cells in 71% of patients. CD8+ TILs were present in tumors from all patients, whereas only 11% of tumors expressed PD-1. There were no correlations between PD-L1 expression and CD8+ TIL abundance, PD-1 expression, or survival.
CONCLUSIONS
Approximately 70% of EBV-positive NPC expressed PD-L1, but this did not correlate with patient survival or clinicopathologic features. The findings of this study represent the immune biomarker profile of confirmed EBV-associated NPC in an endemic region. Since the current clinical development of immune checkpoint inhibitor for NPC is mostly focusing on an EBV-associated tumor, differences in immune biomarker profiles and EBV status of endemic and nonendemic regions should be further explored.
目的
靶向程序性死亡蛋白1/程序性死亡蛋白1配体(PD-1/PD-L1)免疫检查点通路的免疫疗法在早期鼻咽癌(NPC)临床研究中已显示出前景。在此,我们评估了NPC患者中PD-1和PD-L1的表达以及CD8+肿瘤浸润淋巴细胞(TILs)。
材料与方法
通过机构数据库识别2007年1月至2012年12月期间新诊断的NPC患者。在诊断时对存档肿瘤样本测量PD-L1和PD-1表达、EB病毒(EBV)状态以及CD8+TIL数量,并评估它们与包括生存在内的临床病理特征的相关性。
结果
共分析了114例NPC患者。大多数患者(96%)为EBV阳性。69%的患者肿瘤细胞(TCs)中PD-L1表达≥1%,12%的患者TCs中PD-L1表达≥50%,71%的患者TCs或浸润免疫细胞中PD-L1表达≥5%。所有患者的肿瘤中均存在CD8+TILs,而只有11%的肿瘤表达PD-1。PD-L1表达与CD8+TIL丰度、PD-1表达或生存之间无相关性。
结论
约70%的EBV阳性NPC表达PD-L1,但这与患者生存或临床病理特征无关。本研究结果代表了流行地区确诊的EBV相关NPC的免疫生物标志物特征。由于目前NPC免疫检查点抑制剂的临床开发大多聚焦于EBV相关肿瘤,应进一步探索流行地区和非流行地区免疫生物标志物特征及EBV状态的差异。