Monitoring immune-checkpoint blockade: response evaluation and biomarker development.
Monitoring immune-checkpoint blockade: response evaluation and biomarker development.
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DOI：
10.1038/nrclinonc.2017.88
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Hodi FS
中科院分区：
文献类型：
--
作者：
Nishino M;Ramaiya NH;Hatabu H;Hodi FS
使用免疫检查点阻断（ICB）的癌症免疫疗法已经在晚期癌症的治疗中创造了范式转变。靶向免疫检查点蛋白CTLA-4、PD-1和PD-L1的单克隆抗体的有希望的抗肿瘤活性导致监管机构批准这些药物用于治疗各种恶性肿瘤。患者可能会从这些药物的治疗中获得临床益处，尽管肿瘤反应的非常规模式可能被误解为疾病进展，这为评估免疫治疗反应提供了一种新的特异性方法。此外，正在广泛研究可以预测对ICB反应性的生物标志物，以进一步推进精确的免疫治疗。在此，我们回顾了与ICB相关的非常规反应模式的生物学机制，描述了对此类反应进行客观评估的策略，并强调了正在进行的识别生物标志物的努力，以指导ICB治疗。我们提供免疫相关反应评估的最新知识，确定需要进一步研究的未满足需求，并提出未来方向，以最大限度地发挥ICB治疗的益处。
Cancer immunotherapy using immune-checkpoint blockade (ICB) has created a paradigm shift in the treatment of advanced-stage cancers. The promising antitumour activity of monoclonal antibodies targeting the immune-checkpoint proteins CTLA-4, PD-1, and PD-L1 led to regulatory approvals of these agents for the treatment of a variety of malignancies. Patients might experience clinical benefits from treatment with these agents, despite unconventional patterns of tumour response that can be misinterpreted as disease progression, warranting a new, specific approach to evaluate responses to immunotherapy. In addition, biomarkers that can predict responsiveness to ICB are being extensively investigated to further advance precision immunotherapy. Herein, we review the biological mechanisms underlying the unconventional response patterns associated with ICB, describe strategies for the objective assessments of such responses, and also highlight the ongoing efforts to identify biomarkers, in order to guide treatment with ICB. We provide state-of-the-art knowledge of immune-related response evaluations, identify unmet needs requiring further investigations, and propose future directions to maximize the benefits of ICB therapy.
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通讯作者：
Hodi FS