Expression patterns of programmed death ligand 1 correlate with different microenvironments and patient prognosis in hepatocellular carcinoma.
Expression patterns of programmed death ligand 1 correlate with different microenvironments and patient prognosis in hepatocellular carcinoma.
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程序性死亡配体1的表达模式与肝细胞癌的不同微环境和患者预后相关
DOI：
10.1038/s41416-018-0144-4
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发表时间：
2018-07
影响因子：
8.8
通讯作者：
Zheng L
中科院分区：
文献类型：
--
作者：
Liu CQ;Xu J;Zhou ZG;Jin LL;Yu XJ;Xiao G;Lin J;Zhuang SM;Zhang YJ;Zheng L
为了更好地检测PD-L1在肝细胞癌（HCC）中的表达，我们采用酪胺信号放大系统结合免疫组化技术，对453例HCC患者进行了CD 68和PD-L1双染色，分析了PD-L1的表达模式。结果肿瘤细胞（TC）PD-L1表达与患者的总生存期（OS;P= 0.001）和无复发生存期（RFS;P = 0.006）呈负相关，而巨噬细胞（Mφs）PD-L1表达与OS呈正相关（P= 0.017）。多因素分析显示，TC和Mφ上PD-L1的表达均为影响OS的独立预后因素（TC-PD-L1的HR = 1.168，P = 0.004; Mφ-PD-L1的HR = 0.708，P = 0.003）。结论本研究提供了一种新的方法来评估肿瘤微环境中PD-L1的表达，这可能有助于选择抗PD-1/PD-L1免疫治疗的患者。
BackgroundRecent clinical studies have suggested that programmed death ligand 1 (PD-L1) expression in a tumour could be a potential biomarker for PD-L1/PD-1 blockade therapies.MethodsTo better characterise PD-L1 expression in hepatocellular carcinoma (HCC), we analysed its expression patterns in 453 HCC patients by double staining for CD68 and PD-L1 using the Tyramide Signal Amplification Systems combined with immunohistochemistry. We also investigated its correlation with clinical features, prognosis and immune status.ResultsThe results showed that PD-L1 expression on tumour cells (TCs) was negatively associated with patients’ overall survival (OS;P= 0.001) and relapse-free survival (RFS;P= 0.006); however, PD-L1 expression on macrophages (Mφs) was positively correlated with OS (P= 0.017). Multivariate analysis revealed that PD-L1 expression on TCs and Mφs were both independent prognostic factors for OS (hazard ratio (HR) = 1.168,P= 0.004 for TC-PD-L1; HR = 0.708,P= 0.003 for Mφ-PD-L1). Further studies showed that Mφ-PD-L1+tumours exhibited an activated immune microenvironment, with high levels of CD8+T-cell infiltration and immune-related gene expression.ConclusionOur study provided a novel methodology to evaluate PD-L1 expression in the tumour microenvironment, which might help to select patients who would benefit from anti-PD-1/PD-L1 immunotherapies.