Evaluation of PD-L1 expression on vortex-isolated circulating tumor cells in metastatic lung cancer.

Evaluation of PD-L1 expression on vortex-isolated circulating tumor cells in metastatic lung cancer.
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DOI:
10.1038/s41598-018-19245-w
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发表时间:
2018-02-07
期刊:
影响因子:
4.6
通讯作者:
Kulkarni RP
Kulkarni RP
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Dhar M;Wong J;Che J;Matsumoto M;Grogan T;Elashoff D;Garon EB;Goldman JW;Sollier Christen E;Di Carlo D;Kulkarni RP

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转移性非小细胞肺癌(NSCLC)是一种高度致命和免疫原性的恶性肿瘤。尽管已知免疫系统识别这些肿瘤细胞,但NSCLC可以逃避免疫系统的一种机制是通过程序性细胞死亡配体1(PD-L1)的过表达。最近的PD-1和PD-L1抑制剂的临床试验已经返回了有希望的临床反应。对于个性化治疗来说,肿瘤活检中PD-L1染色强度较高的患者反应更好。因此,人们对使用PD-L1肿瘤表达作为患者选择的标准感兴趣。目前可用的筛查方法包括侵入性肿瘤活检,然后对PD-L1水平进行组织学分级。活检具有高并发症风险,并且仅允许从有限的肿瘤切片中取样,这可能无法反映整体肿瘤异质性。循环肿瘤细胞(CTC)PD-L1水平可以帮助筛查患者,并可以通过检测播散性肿瘤部位的PD-L1表达来补充组织PD-L1活检结果。为了建立CTC作为筛选工具,我们开发了一种方案来分离高纯度的CTC并对PD-L1进行免疫染色。监测CTC上的PD-L1表达可能是精确医学的另一个生物标志物,可以帮助确定对免疫疗法的反应。
Metastatic non-small cell lung cancer (NSCLC) is a highly fatal and immunogenic malignancy. Although the immune system is known to recognize these tumor cells, one mechanism by which NSCLC can evade the immune system is via overexpression of programmed cell death ligand 1 (PD-L1). Recent clinical trials of PD-1 and PD-L1 inhibitors have returned promising clinical responses. Important for personalizing therapy, patients with higher intensity staining for PD-L1 on tumor biopsies responded better. Thus, there has been interest in using PD-L1 tumor expression as a criterion for patient selection. Currently available methods of screening involve invasive tumor biopsy, followed by histological grading of PD-L1 levels. Biopsies have a high risk of complications, and only allow sampling from limited tumor sections, which may not reflect overall tumor heterogeneity. Circulating tumor cell (CTC) PD-L1 levels could aid in screening patients, and could supplement tissue PD-L1 biopsy results by testing PD-L1 expression from disseminated tumor sites. Towards establishing CTCs as a screening tool, we developed a protocol to isolate CTCs at high purity and immunostain for PD-L1. Monitoring of PD-L1 expression on CTCs could be an additional biomarker for precision medicine that may help in determining response to immunotherapies.
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