Nimmagadda Sridhar
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Cancers (Basel). 2020 Oct 29;12(11):3173. doi: 10.3390/cancers12113173.
Therapeutics targeting programmed death ligand 1 (PD-L1) protein and its receptor PD-1 are now dominant players in restoring anti-tumor immune responses. PD-L1 detection by immunohistochemistry (IHC) is emerging as a reproducible biomarker for guiding patient stratification for those therapies in some cancers. However, PD-L1 expression in the tumor microenvironment is highly complex. It is upregulated by aberrant genetic alterations, and is highly regulated at the transcriptional, posttranscriptional, and protein levels. Thus, PD-L1 IHC is inadequate to fully understand the relevance of PD-L1 levels in the whole body and their dynamics to improve therapeutic outcomes. Imaging technologies could potentially assist in meeting that need. Early clinical investigations show promising results in quantifying PD-L1 expression in the whole body by positron emission tomography (PET). Within this context, this review summarizes advancements in regulation of PD-L1 expression and imaging agents, and in PD-L1 PET for drug development, and discusses opportunities and challenges presented by these innovations for guiding immune checkpoint therapy (ICT).
靶向程序性死亡配体1（PD-L1）蛋白及其受体PD-1的疗法目前在恢复抗肿瘤免疫反应方面占据主导地位。通过免疫组织化学（IHC）检测PD-L1正在成为一种可重复的生物标志物，用于指导某些癌症患者接受这些疗法的分层治疗。然而，肿瘤微环境中的PD-L1表达非常复杂。它通过异常的基因改变而上调，并且在转录、转录后和蛋白质水平上受到高度调控。因此，PD-L1免疫组化不足以充分了解全身PD-L1水平及其动态变化与改善治疗效果的相关性。成像技术可能有助于满足这一需求。早期临床研究显示，正电子发射断层扫描（PET）在定量全身PD-L1表达方面取得了有前景的结果。在此背景下，本综述总结了PD-L1表达调控和成像剂以及用于药物开发的PD-L1 PET方面的进展，并讨论了这些创新为指导免疫检查点疗法（ICT）带来的机遇和挑战。
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