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循环肿瘤细胞程序性死亡受体配体 1 在肺癌患者中的异质性表达。

Heterogeneous Expression of Programmed Death Receptor-ligand 1 on Circulating Tumor Cells in Patients With Lung Cancer.

机构信息

Internal Medicine III, Wakayama Medical University, Wakayama, Japan.

Medical Business Unit, Hitachi Chemical Co, Ltd, Ibaraki, Japan.

出版信息

Clin Lung Cancer. 2019 Jul;20(4):270-277.e1. doi: 10.1016/j.cllc.2019.03.004. Epub 2019 Mar 25.

Abstract

BACKGROUND

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.

MATERIALS AND METHODS

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.

RESULTS

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).

CONCLUSION

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.

摘要

背景

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。

材料与方法

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。

结果

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)。

结论

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。

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