Frequent expression of PD-L1 on circulating breast cancer cells
Frequent expression of PD-L1 on circulating breast cancer cells
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DOI：
10.1016/j.molonc.2015.05.009
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发表时间：
2015-11-01
影响因子：
6.6
通讯作者：
Alix-Panabieres, Catherine
中科院分区：
文献类型：
--
作者：
Mazel, Martine;Jacot, William;Alix-Panabieres, Catherine
免疫检查点调节剂（如PD-L1）已成为令人兴奋的新治疗靶点，可使晚期恶性肿瘤患者获得长期缓解。然而，鉴于这些疗法的显著成本和毒性特征，迫切需要能够区分应答者和非应答者的预测性生物标志物。在本文中，我们提供的证据表明，PD-L1经常在激素受体阳性，HER 2阴性乳腺癌患者血液中循环的转移细胞上表达。我们进行了蛋白质印迹，流式细胞术和免疫细胞化学分析，以证明我们的研究中使用的PDL 1抗体的特异性，并建立了单个肿瘤细胞上PDL 1表达的免疫评分。然后，我们使用CellSearch（R）系统选择了16名具有循环肿瘤细胞（CTC）的患者，并在11名患者（68.8%）中发现了PD-L1（（+））CTC。个体患者中PD-L1（（+））CTC的分数从0.2%至100%不等。这是第一份证明PD-L1在CTC上表达的报告。已建立的CTC/PD-L1检测可在未来的临床试验中用于液体活检，以分层和监测接受免疫检查点阻断的癌症患者。(c)2015年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Immune checkpoint regulators such as PD-L1 have become exciting new therapeutic targets leading to long lasting remissions in patients with advanced malignancies. However, in view of the remarkable costs and the toxicity profiles of these therapies, predictive biomarkers able to discriminate responders from non-responders are urgently needed. In the present paper, we provide evidence that PD-L1 is frequently expressed on metastatic cells circulating in the blood of hormone receptor-positive, HER2-negative breast cancer patients. We performed western blot, flow cytometry and immunocytochemical analyses to demonstrate the specificity of the PDL1 antibody used in our study and established immunoscores for PDL1 expression on single tumor cells. We then selected sixteen patients with circulating tumor cells (CTCs) using the CellSearch (R) system and found PD-L1((+)) CTCs in 11 patients (68.8%). The fraction of PD-L1((+)) CTCs varied from 0.2 to 100% in individual patients. This is the first report demonstrating the expression of PD-L1 on CTCs. The established CTC/PD-L1 assay can be used for liquid biopsy in future clinical trials for stratification and monitoring of cancer patients undergoing immune checkpoint blockade. (c) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.