检测晚期非小细胞肺癌患者循环肿瘤细胞和白细胞中的 PD-L1。
Detection of PD-L1 in circulating tumor cells and white blood cells from patients with advanced non-small-cell lung cancer.
机构信息
University Hospital Federation OncoAge, CHU de Nice, Nice, France.
Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.
出版信息
Ann Oncol. 2018 Jan 1;29(1):193-199. doi: 10.1093/annonc/mdx636.
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.
背景
肿瘤细胞和肿瘤浸润免疫细胞中 PD-L1 的表达与接受抗 PD-1/PD-L1 抑制剂治疗的晚期非小细胞肺癌（NSCLC）患者的疗效改善相关，并且已成为选择癌症免疫疗法患者的潜在生物标志物。我们研究了循环肿瘤细胞（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（ISET®平台；Rarecells）中富集 CTCs 和循环 WBCs。通过自动免疫染色（SP142 抗体；Ventana）评估 ISET 滤器和匹配肿瘤组织上的 PD-L1 表达，并在肿瘤细胞和 WBCs 中进行定量。
结果
80 名（75%）患者检测到 CTCs，水平范围为 2 至 256 CTCs/4ml，中位数为 60 CTCs/4ml。在 71 个具有匹配组织和 CTCs 的可评估样本中，6 名患者（8%）的 CTCs 中≥1 个 PD-L1 阳性，11 名患者（15%）的肿瘤组织中≥1%的肿瘤细胞 PD-L1 阳性，组织与 CTCs 的一致性为 93%（敏感性=55%；特异性=100%）。在 74 个具有匹配组织和循环 WBCs 的样本中，40 名患者（54%）的肿瘤组织中≥1%的免疫浸润 PD-L1 阳性，39 名患者（53%）的循环 WBCs 中≥1%的 PD-L1 阳性，血液与组织的一致性为 80%（敏感性=82%；特异性=79%）。我们发现，在接受一线顺铂为基础的化疗治疗的患者中，其肿瘤在 CTCs 或免疫细胞中表达 PD-L1 时，生存时间更差（无进展和总生存），与匹配患者肿瘤中 PD-L1 表达的效果相似。
结论
这些结果表明，CTC 和循环 WBCs 中的 PD-L1 状态与肿瘤组织中的 PD-L1 状态相关，揭示了 CTCs 评估作为一种非侵入性实时活检的潜力，用于评估晚期 NSCLC 患者的 PD-L1 表达。
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