Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy.
Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy.
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DOI：
10.1186/s13045-016-0277-y
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发表时间：
2016-05-27
影响因子：
28.5
通讯作者：
Li T
中科院分区：
文献类型：
--
作者：
Ma W;Gilligan BM;Yuan J;Li T
调节免疫抑制途径是癌症治疗最近的一项重大突破。靶向细胞毒性T淋巴细胞抗原4（CTLA-4）和程序性细胞死亡蛋白1（PD-1）的检查点阻断抗体已在一些晚期黑色素瘤、非小细胞肺癌（NSCLC）和其他肿瘤类型患者中显示出可接受的毒性、有希望的临床反应、持久的疾病控制和改善的生存期。约20%的晚期NSCLC患者和30%的晚期黑色素瘤患者经历了检查点阻断单药治疗的肿瘤应答，抗PD-1和抗CTLA-4抗体联合治疗的临床应答更好。鉴于这些新疗法的强大功能，重要的是要了解宿主免疫反应的复杂性和动态性，以及肿瘤微环境和正常器官中其他分子对检查点阻断疗法的反应。在这个精确肿瘤学的时代，仍然存在很大程度上未满足的需求，以确定最有可能从免疫治疗中受益的患者，优化肿瘤特异性免疫应答的监测测定，开发提高临床疗效的策略，并确定生物标志物，从而避免免疫相关的不良事件。目前，使用22 C3抗体进行的PD-L1免疫组织化学（IHC）染色是FDA批准的唯一用于NSCLC治疗pembrolizumab患者的伴随诊断方法，但预计将有更多产品上市。我们在这里总结了目前的知识，临床疗效，潜在的免疫生物标志物，并在先进的实体瘤免疫检查点阻断疗法的相关测定。
Modulating immune inhibitory pathways has been a major recent breakthrough in cancer treatment. Checkpoint blockade antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programed cell-death protein 1 (PD-1) have demonstrated acceptable toxicity, promising clinical responses, durable disease control, and improved survival in some patients with advanced melanoma, non-small cell lung cancer (NSCLC), and other tumor types. About 20 % of advanced NSCLC patients and 30 % of advanced melanoma patients experience tumor responses from checkpoint blockade monotherapy, with better clinical responses seen with the combination of anti-PD-1 and anti-CTLA-4 antibodies. Given the power of these new therapies, it is important to understand the complex and dynamic nature of host immune responses and the regulation of additional molecules in the tumor microenvironment and normal organs in response to the checkpoint blockade therapies. In this era of precision oncology, there remains a largely unmet need to identify the patients who are most likely to benefit from immunotherapy, to optimize the monitoring assays for tumor-specific immune responses, to develop strategies to improve clinical efficacy, and to identify biomarkers so that immune-related adverse events can be avoided. At this time, PD-L1 immunohistochemistry (IHC) staining using 22C3 antibody is the only FDA-approved companion diagnostic for patients with NSCLC-treated pembrolizumab, but more are expected to come to market. We here summarize the current knowledge, clinical efficacy, potential immune biomarkers, and associated assays for immune checkpoint blockade therapies in advanced solid tumors.