Next generation predictive biomarkers for immune checkpoint inhibition.
Next generation predictive biomarkers for immune checkpoint inhibition.
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DOI：
10.1007/s10555-016-9652-y
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Patel SP
中科院分区：
文献类型：
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作者：
Khagi Y;Kurzrock R;Patel SP
随着靶向治疗的出现，在多种组织学的癌症治疗方面发生了一场革命。免疫检查点阻断使得在广泛的恶性肿瘤中利用免疫细胞和肿瘤细胞之间的受体-配体相互作用成为可能。然而，健康组织中的毒性会限制我们使用这些药物。免疫检查点阻断已被批准用于晚期黑色素瘤、肾细胞癌、非小细胞肺癌、复发难治性霍奇金淋巴瘤和尿路上皮癌。尽管fda批准的一些新药物的适应症依赖于当前基于蛋白质的PD1和PD-L1检测，但检测方法有几个警告。必须使用额外的预测工具来区分反应者和非反应者。其中包括微卫星不稳定性、PD-L1扩增、CD8浸润密度和肿瘤突变负荷的测量。本综述旨在合成DNA、RNA和蛋白质水平的生物标志物检测，以更准确地预测这些新药物的疗效。
With the advent of targeted therapies, there has been a revolution in the treatment of cancer across multiple histologies. Immune checkpoint blockade has made it possible to take advantage of receptor-ligand interactions between immune and tumor cells in a wide spectrum of malignancies. Toxicity in healthy tissue, however, can limit our use of these agents. Immune checkpoint blockade has been approved in advanced melanoma, renal cell cancer, non-small cell lung cancer, relapsed refractory Hodgkin's lymphoma, and urothelial cancer. Though FDA-approved indications for use of some of these novel agents depend on current, protein-based PD1 and PD-L1 assays, detection methods come with several caveats. Additional predictive tools must be interrogated to discern responders from non-responders. Some of these include measurement of microsatellite instability, PD-L1 amplification, CD8 infiltrate density, and tumor mutational burden. This review serves to synthesize biomarker detection at the DNA, RNA, and protein level to more accurately forecast benefit from these novel agents.