Internal Medicine III, Wakayama Medical University, Wakayama, Japan.
Medical Business Unit, Hitachi Chemical Co, Ltd, Ibaraki, Japan.
Clin Lung Cancer. 2019 Jul;20(4):270-277.e1. doi: 10.1016/j.cllc.2019.03.004. Epub 2019 Mar 25.
Blockade of the programmed death receptor-1 (PD-1) pathway is effective against solid tumors including lung cancer. PD-ligand 1 (PD-L1) expression on tumor tissue serves as a predictive biomarker for the efficacy of PD-1 pathway blockade. Here, we evaluated the expression of PD-L1 on circulating tumor cells (CTCs) in patients with lung cancer.
Peripheral whole blood (3 mL) was collected from patients, and CTCs and PD-L1 expression were detected using a microcavity array (MCA) system. Immunohistochemistry for PD-L1 detection was also performed using matched tumor tissues.
Sixty-seven patients with lung cancer were enrolled in the study between July 2015 and April 2016 at Wakayama Medical University Hospital. The characteristics of the patients were as follows: median age, 71 years (range, 39-86 years); male, 72%; stage II to III/IV, 14%/85%; non-small-cell lung cancer/small-cell lung cancer/other, 73%/21%/6%. CTCs were detected in 66 of 67 patients (median, 19; range, 0-115), and more than 5 CTCs were detected in 78% of patients. PD-L1-expressing CTCs were detected in 73% of patients, and the proportion score of PD-L1-expressing CTCs ranged from 3% to 100%, suggesting intra-patient heterogeneity of PD-L1 expression on CTCs. Tumor tissues were available from 27 patients and were immunostained for PD-L1, and no correlation was observed between tumor tissues and CTCs based on the proportion score (R = 0.0103).
PD-L1 expression was detectable on CTCs in patients with lung cancer, and intra-patient heterogeneity was observed. No correlation was observed between PD-L1 expression in tumor tissues and CTCs.
程序性死亡受体-1（PD-1）通路的阻断对包括肺癌在内的实体瘤有效。肿瘤组织中 PD-配体 1（PD-L1）的表达可作为 PD-1 通路阻断疗效的预测生物标志物。在此，我们评估了肺癌患者循环肿瘤细胞（CTC）中 PD-L1 的表达。
从患者采集外周全血（3 毫升），并使用微腔阵列（MCA）系统检测 CTC 和 PD-L1 表达。还使用匹配的肿瘤组织进行 PD-L1 检测的免疫组织化学分析。
2015 年 7 月至 2016 年 4 月，我们在和歌山县立医科大学医院共招募了 67 例肺癌患者。患者的特征如下：中位年龄 71 岁（范围，39-86 岁）；男性，72%；II 期至 III/IV 期，14%/85%；非小细胞肺癌/小细胞肺癌/其他，73%/21%/6%。67 例患者中有 66 例（中位数，19；范围，0-115）检测到 CTC，78%的患者检测到超过 5 个 CTC。73%的患者检测到 PD-L1 表达的 CTC，PD-L1 表达的 CTC 的比例评分范围为 3%至 100%，提示 CTC 上 PD-L1 表达存在患者内异质性。27 例患者的肿瘤组织可用于 PD-L1 免疫染色，并且根据比例评分观察到肿瘤组织与 CTC 之间无相关性（R=0.0103）。
在肺癌患者的 CTC 中可检测到 PD-L1 表达，并观察到患者内异质性。肿瘤组织中 PD-L1 表达与 CTC 之间无相关性。
