Cancer Research Center, Qatar Biomedical Research Institute, College of Science and Engineering, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar.
Institute of Cancer Sciences, University of Manchester, Manchester, UK.
Exp Mol Med. 2018 Dec 13;50(12):1-11. doi: 10.1038/s12276-018-0191-1.
Cancer growth and progression are associated with immune suppression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. Monoclonal antibodies that target immune checkpoints provided an immense breakthrough in cancer therapeutics. Among the immune checkpoint inhibitors, PD-1/PD-L1 and CTLA-4 inhibitors showed promising therapeutic outcomes, and some have been approved for certain cancer treatments, while others are under clinical trials. Recent reports have shown that patients with various malignancies benefit from immune checkpoint inhibitor treatment. However, mainstream initiation of immune checkpoint therapy to treat cancers is obstructed by the low response rate and immune-related adverse events in some cancer patients. This has given rise to the need for developing sets of biomarkers that predict the response to immune checkpoint blockade and immune-related adverse events. In this review, we discuss different predictive biomarkers for anti-PD-1/PD-L1 and anti-CTLA-4 inhibitors, including immune cells, PD-L1 overexpression, neoantigens, and genetic and epigenetic signatures. Potential approaches for further developing highly reliable predictive biomarkers should facilitate patient selection for and decision-making related to immune checkpoint inhibitor-based therapies.
癌症的生长和进展与免疫抑制有关。癌细胞有能力激活具有免疫抑制功能的不同免疫检查点途径。针对免疫检查点的单克隆抗体为癌症治疗提供了巨大的突破。在免疫检查点抑制剂中，PD-1/PD-L1 和 CTLA-4 抑制剂显示出有希望的治疗效果，其中一些已被批准用于某些癌症治疗，而其他则在临床试验中。最近的报告表明，患有各种恶性肿瘤的患者从免疫检查点抑制剂治疗中获益。然而，由于某些癌症患者的低反应率和免疫相关不良事件，主流的免疫检查点治疗开始受到阻碍。这就需要开发一系列预测标志物，以预测对免疫检查点阻断和免疫相关不良事件的反应。在这篇综述中，我们讨论了抗 PD-1/PD-L1 和抗 CTLA-4 抑制剂的不同预测生物标志物，包括免疫细胞、PD-L1 过表达、新抗原和遗传及表观遗传特征。进一步开发高度可靠的预测生物标志物的潜在方法，应有助于患者选择和决策与免疫检查点抑制剂为基础的治疗相关。
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