Larbcharoensub Noppadol, Mahaprom Komkrit, Jiarpinitnun Chuleeporn, Trachu Narumol, Tubthong Nattha, Pattaranutaporn Poompis, Sirachainan Ekaphop, Ngamphaiboon Nuttapong
Department of Pathology.
Department of Medicine, Division of Medical Oncology.
Am J Clin Oncol. 2018 Dec;41(12):1204-1210. doi: 10.1097/COC.0000000000000449.
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.
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.
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.
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.
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）。
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。
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。
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。
