Background Expression of PD-L1 in tumor cells and tumor-infiltrating immune cells has been associated with improved efficacy to anti-PD-1/PD-L1 inhibitors in patients with advanced-stage non-small-cell lung cancer (NSCLC) and emerged as a potential biomarker for the selection of patients to cancer immunotherapies. We investigated the utility of circulating tumor cells (CTCs) and circulating white blood cells (WBCs) as a noninvasive method to evaluate PD-L1 status in advanced NSCLC patients. Patients and methods CTCs and circulating WBCs were enriched from peripheral blood samples (ISET® platform; Rarecells) from 106 NSCLC patients. PD-L1 expression on ISET filters and matched-tumor tissue was evaluated by automated immunostaining (SP142 antibody; Ventana), and quantified in tumor cells and WBCs. Results CTCs were detected in 80 (75%) patients, with levels ranging from 2 to 256 CTCs/4 ml, and median of 60 CTCs/4 ml. Among 71 evaluable samples with matched-tissue and CTCs, 6 patients (8%) showed ≥1 PD-L1-positive CTCs and 11 patients (15%) showed ≥1% PD-L1-positive tumor cells in tumor tissue with 93% concordance between tissue and CTCs (sensitivity = 55%; specificity = 100%). From 74 samples with matched-tissue and circulating WBCs, 40 patients (54%) showed ≥1% PD-L1-positive immune infiltrates in tumor tissue and 39 patients (53%) showed ≥1% PD-L1 positive in circulating WBCs, with 80% concordance between blood and tissue (sensitivity = 82%; specificity = 79%). We found a trend for worse survival in patients receiving first-line cisplatin-based chemotherapy treatments, whose tumors express PD-L1 in CTCs or immune cells (progression-free and overall survival), similar to the effects of PD-L1 expression in matched-patient tumors. Conclusions These results demonstrated that PD-L1 status in CTCs and circulating WBCs correlate with PD-L1 status in tumor tissue, revealing the potential of CTCs assessment as a noninvasive real-time biopsy to evaluate PD-L1 expression in patients with advanced-stage NSCLC.

中文翻译：

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晚期非小细胞肺癌患者循环肿瘤细胞和白细胞中PD-L1的检测。

背景PD-L1在肿瘤细胞和浸润性免疫细胞中的表达与晚期非小细胞肺癌（NSCLC）患者抗PD-1 / PD-L1抑制剂的疗效改善相关，并且已经出现作为选择癌症免疫疗法患者的潜在生物标志物。我们调查了循环肿瘤细胞（CTC）和循环白细胞（WBC）作为评估晚期NSCLC患者PD-L1状态的一种非侵入性方法的实用性。患者和方法从106名NSCLC患者的外周血样本（平台； Rarecells）中富集了四氯化碳和循环白细胞。通过自动免疫染色（SP142抗体； Ventana）评估ISET过滤器和匹配的肿瘤组织上的PD-L1表达，并在肿瘤细胞和WBC中进行定量。结果80例患者中检出了四氯化碳（75％），含量范围从2到256 CTCs / 4 ml，中位数为60 CTCs / 4 ml。在71个组织和CTC匹配的可评估样本中，肿瘤组织中6例（8％）的PD-L1阳性CTCs和11例（15％）≥1％的PD-L1阳性肿瘤细胞，其中93％组织与CTC之间的一致性（敏感性= 55％；特异性= 100％）。在74个组织和循环白细胞相匹配的样本中，有40例（54％）的肿瘤组织中PD-L1阳性免疫浸润≥1％，而39例（53％）的循环WBC中的PD-L1阳性≥1％，血液和组织之间的一致性达到80％（敏感性= 82％；特异性= 79％）。我们发现接受基于顺铂的一线化疗的一线治疗患者的生存恶化趋势，这些患者的肿瘤在CTC或免疫细胞中表达PD-L1（无进展生存期和总生存期），与PD-L1表达在匹配患者肿瘤中的作用相似。结论这些结果表明，CTC和循环中的WBC中PD-L1的状态与肿瘤组织中PD-L1的状态相关，揭示了CTC评估作为无创实时活检评估晚期NSCLC患者PD-L1表达的潜力。 。