Vathiotis Ioannis A, MacNeil Tyler, Zugazagoitia Jon, Syrigos Konstantinos N, Aung Thazin Nwe, Gruver Aaron M, Vaillancourt Peter, Hughes Ina, Hinton Steve, Driscoll Kyla, Rimm David L
Department of Pathology, BML 116, Yale University School of Medicine, 310 Cedar St. P.O. Box 208023, New Haven, CT 06520-8023, USA.
Department of Medicine, National and Kapodistrian University of Athens School of Medicine, 11527 Athens, Greece.
Cancers (Basel). 2021 Mar 1;13(5):1024. doi: 10.3390/cancers13051024.
CD200/CD200R is an immune checkpoint with broad expression patterns and a potential target for immune therapy. In this study, we assess both CD200 and CD200R expression in solid tumors, with a focus on lung cancer, and evaluate their association with clinicopathologic characteristics, mutation status, outcome, and programmed death-ligand 1 (PD-L1) expression. We used multiplexed quantitative immunofluorescence (QIF) to measure the expression of CD200 and CD200R in a total of 455 patients from three lung cancer cohorts. Using carefully validated antibodies, we performed target measurement with tyramide-based QIF panels and analyzed the data using the PM2000 microscope and AQUA software. CD200 tumor positivity was found in 29.7% of non-small cell lung cancer (NSCLC) patients and 33.3% of lung large cell neuroendocrine carcinoma (LCNEC) patients. CD200 demonstrated notable intratumoral heterogeneity. CD200R was expressed in immune cells in 25% of NSCLC and 41.3% of LCNEC patients. While CD200R is predominantly expressed in immune cells, rare tumor cell staining was seen in a highly heterogeneous pattern. CD200R expression in the stromal compartment was significantly higher in patients with squamous differentiation ( < 0.0001). Neither CD200 nor CD200R were associated with other clinicopathologic characteristics or mutation status. Both biomarkers were not prognostic for disease-free or overall survival in NSCLC. CD200 showed moderate correlation with PD-L1. CD200/CD200R pathway is frequently expressed in lung cancer patients. Differential expression patterns of CD200 and CD200R with PD-L1 suggest a potential role for targeting this pathway alone in patients with NSCLC.
CD200/CD200R是一种具有广泛表达模式的免疫检查点，也是免疫治疗的潜在靶点。在本研究中，我们评估了实体瘤中CD200和CD200R的表达情况，重点是肺癌，并评估它们与临床病理特征、突变状态、预后以及程序性死亡配体1（PD-L1）表达之间的关联。我们使用多重定量免疫荧光（QIF）技术，对来自三个肺癌队列的总共455例患者的CD200和CD200R表达进行了检测。我们使用经过严格验证的抗体，通过基于酪胺的QIF检测板进行靶点测量，并使用PM2000显微镜和AQUA软件对数据进行分析。在29.7%的非小细胞肺癌（NSCLC）患者和33.3%的肺大细胞神经内分泌癌（LCNEC）患者中发现了CD200肿瘤阳性。CD200表现出显著的肿瘤内异质性。在25%的NSCLC患者和41.3%的LCNEC患者的免疫细胞中表达了CD200R。虽然CD200R主要在免疫细胞中表达，但在高度异质性模式下可见罕见的肿瘤细胞染色。鳞状分化患者基质区室中的CD200R表达显著更高（<0.0001）。CD200和CD200R均与其他临床病理特征或突变状态无关。这两种生物标志物对NSCLC患者的无病生存期或总生存期均无预后价值。CD200与PD-L1呈中度相关。CD200/CD200R通路在肺癌患者中经常表达。CD200和CD200R与PD-L1的差异表达模式表明，单独靶向该通路在NSCLC患者中可能具有潜在作用。
