Predictive biomarkers for checkpoint inhibitor-based immunotherapy.
Predictive biomarkers for checkpoint inhibitor-based immunotherapy.
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DOI：
10.1016/s1470-2045(16)30406-5
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发表时间：
2016-12
期刊：
影响因子：
--
通讯作者：
Atkins MB
中科院分区：
文献类型：
--
作者：
Gibney GT;Weiner LM;Atkins MB
基于检查点抑制剂的免疫治疗的临床发展开启了一个令人兴奋的抗癌治疗时代。在黑色素瘤和其他恶性肿瘤患者中可以看到持久的反应。虽然PD-1或PD-L1药物的单一治疗通常耐受性良好，但联合用药会增加与免疫相关的不良事件的风险。需要开发预测生物标记物来优化患者的利益，将毒性风险降至最低，并指导联合治疗方法。最大的焦点一直是肿瘤细胞PD-L1的表达。虽然PD-L1阳性在具有临床益处的人群中得到丰富，但在大多数恶性肿瘤中，仅有PD-L1检测不足以用于患者选择。在这篇综述中，我们讨论了PD-L1检测的现状，并探索了肿瘤浸润性淋巴细胞、突变负荷、免疫基因信号和多重免疫组织化学等新的生物标记物策略的新数据。基于检查点抑制剂的免疫治疗的有效预测生物标记物的未来发展将整合多种方法来优化免疫肿瘤微环境的特征。
The clinical development of checkpoint inhibitor-based immunotherapy has ushered in an exciting era of anticancer therapy. Durable responses can be seen in patients with melanoma and other malignancies. Although monotherapy with PD-1 or PD-L1 agents are typically well tolerated, the risk of immune-related adverse events increases with combination regimens. The development of predictive biomarkers is needed to optimise patient benefit, minimise risk of toxicities, and guide combination approaches. The greatest focus has been on tumour-cell PD-L1 expression. Although PD-L1 positivity enriches for populations with clinical benefit, PD-L1 testing alone is insufficient for patient selection in most malignancies. In this Review, we discuss the status of PD-L1 testing and explore emerging data on new biomarker strategies with tumour-infiltrating lymphocytes, mutational burden, immune gene signatures, and multiplex immunohistochemistry. Future development of an effective predictive biomarker for checkpoint inhibitor-based immunotherapy will integrate multiple approaches for optimal characterisation of the immune tumour microenvironment.