Wu Fei, Gu Yanzi, Kang Bin, Heskia Fabienne, Pachot Alexandre, Bonneville Marc, Wei Ping, Liang Ji
Fudan University Shanghai Cancer Center-Institut Mérieux Laboratory, Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.
bioMérieux (Shanghai) Company Limited, Shanghai, China.
Transl Lung Cancer Res. 2021 Jun;10(6):2441-2451. doi: 10.21037/tlcr-20-1277.
Recent breakthroughs in therapies with immune checkpoint inhibitors (ICIs) have revolutionized the treatment of lung cancer. However, only 15-25% of patients respond to the ICIs therapy, and methods to identify those responsive patients are currently a hot research topic. PD-L1 expression measured on tumor tissues using immunohistochemistry (IHC) was approved as one of the companion diagnostic methods, but it is invasive and cannot be used to monitor dynamic changes in PD-L1 expression during treatments.
In this study, we developed an Epcam-PD-L1 extracellular vesicle (EV) detection prototype using the Simoa platform. This assay detected PD-L1 expression levels on tumor-derived exosomes from the lung cancer cell lines A549 and SK-MES1. In addition, 35 plasma samples from patients with lung cancer were tested with this assay and the results were compared to the tissue PD-L1 expression levels represented by the tumor proportion score (TPS).
PD-L1 TPS-positive patients (≥1% IHC TPS) had significantly higher Simoa Epcam-PD-L1 signals than TPS-negative patients (<1% IHC TPS, P=0.026). The Simoa Epcam-PD-L1 area under curve (AUC) reached 0.776, with a sensitivity of 92.86% and a specificity of 71.43%. When PD-L1 TPS-positive patients were defined as having an IHC TPS ≥10%, the greatest difference in Epcam-PD-L1 signals was observed between IHC TPS-positive and IHC TPS-negative groups (P=0.0024) and the Simoa Epcam-PD-L1 AUC reached 0.832. Finally, the Spearman's correlation coefficient showed a significant correlation between the TPS and Simoa Epcam-PD-L1 signals (0.428, P=0.0104).
Based on our results, our Simoa Epcam-PD-L1 EV detection assay is a potential liquid biopsy method to predict the PD-L1 expression level in patients with lung cancer.
免疫检查点抑制剂（ICI）疗法的近期突破彻底改变了肺癌的治疗方式。然而，只有15%至25%的患者对ICI疗法有反应，识别那些有反应患者的方法目前是一个热门研究课题。使用免疫组织化学（IHC）在肿瘤组织上测量的PD-L1表达被批准为伴随诊断方法之一，但它具有侵入性，且不能用于监测治疗期间PD-L1表达的动态变化。
在本研究中，我们使用Simoa平台开发了一种Epcam-PD-L1细胞外囊泡（EV）检测原型。该检测方法检测了肺癌细胞系A549和SK-MES1肿瘤来源外泌体上的PD-L1表达水平。此外，用该检测方法对35例肺癌患者的血浆样本进行了检测，并将结果与肿瘤比例评分（TPS）所代表的组织PD-L1表达水平进行了比较。
PD-L1 TPS阳性患者（≥1% IHC TPS）的Simoa Epcam-PD-L1信号显著高于TPS阴性患者（<1% IHC TPS，P = 0.026）。Simoa Epcam-PD-L1曲线下面积（AUC）达到0.776，敏感性为92.86%，特异性为71.43%。当将PD-L1 TPS阳性患者定义为IHC TPS≥10%时，在IHC TPS阳性和IHC TPS阴性组之间观察到Epcam-PD-L1信号的最大差异（P = 0.0024），且Simoa Epcam-PD-L1 AUC达到0.832。最后，Spearman相关系数显示TPS与Simoa Epcam-PD-L1信号之间存在显著相关性（0.428，P = 0.0104）。
基于我们的结果，我们的Simoa Epcam-PD-L1 EV检测方法是一种预测肺癌患者PD-L1表达水平的潜在液体活检方法。
