Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy.
Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy.
复制标题
机制驱动的生物标志物指导癌症治疗中的免疫检查点阻断。
DOI：
10.1038/nrc.2016.36
复制
发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Pardoll DM
中科院分区：
文献类型：
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作者：
Topalian SL;Taube JM;Anders RA;Pardoll DM
随着最近批准用于阻断黑色素瘤、非小细胞肺癌和肾癌中的细胞毒性T淋巴细胞相关抗原4（CTLA4）和程序性细胞死亡蛋白1（PD1）的多种治疗性抗体，以及临床上靶向的另外的免疫检查点，关于阻断这些检查点途径的药物的最佳使用仍然存在许多问题。定义预测治疗效果和不良事件的生物标志物是一项至关重要的任务，最近批准的两项PDL 1诊断测试突出了这一点。在这里，我们讨论了基于免疫学，遗传学和病毒学标准的抗PD1治疗的生物标志物。与PD1相比，CTLA4免疫检查点的独特生物学需要不同的生物标志物开发方法。来自这些研究的基于机制的见解可以指导基于免疫检查点阻断的协同治疗组合的设计。
With recent approvals for multiple therapeutic antibodies that block cytotoxic T lymphocyte associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) in melanoma, non-small-cell lung cancer and kidney cancer, and additional immune checkpoints being targeted clinically, many questions still remain regarding the optimal use of drugs that block these checkpoint pathways. Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate, highlighted by recent approvals for two PDL1 diagnostic tests. Here, we discuss biomarkers for anti-PD1 therapy based on immunological, genetic and virological criteria. The unique biology of the CTLA4 immune checkpoint, compared with PD1, requires a different approach to biomarker development. Mechanism-based insights from such studies may guide the design of synergistic treatment combinations based on immune checkpoint blockade.