PD-L1 and immune escape: insights from melanoma and other lineage-unrelated malignancies
PD-L1 and immune escape: insights from melanoma and other lineage-unrelated malignancies
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DOI：
10.1016/j.humpath.2017.06.012
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发表时间：
2017-08-01
期刊：
影响因子：
3.3
通讯作者：
Mahalingam, Meera
中科院分区：
文献类型：
--
作者：
Frydenlund, Noah;Mahalingam, Meera
过去十年肿瘤学的重大突破之一是免疫检查点抑制剂的研发。自从发现 PD-1/PD-L1 轴作为外周自我耐受的关键介质，以及随后发现其在癌症中促进免疫逃逸的作用以来，PD-1/PD-L1 通路从科学和治疗的角度都引起了相当大的兴奋。过去十年，使用抗 PD-1/PD-L1 疗法的临床试验数量激增。值得注意的是，病理学家在这些试验的开展以及在 FDA 批准的临床环境中指导抗 PD-1/PD-L1 疗法的使用方面发挥了关键作用。组织活检分析已越来越多地用于预测哪些癌症患者最有可能从这些新疗法中受益。然而，在快速变化的治疗和科学领域仍然存在许多悬而未决的问题。在这篇综述中，我们描述了正常生物学中 PD-1/PD-L1 轴的基本功能，它如何被癌症利用来促进免疫逃逸，然后回顾了有关肿瘤 PD-L1 表达本身的预后价值的文献，然后讨论了最新的治疗进展，以及病理学家在预测抗 PD-1/PD-L1 疗法的反应中的新作用。特别关注黑色素瘤和非小细胞肺癌，抗 PD-L1/PD-1 疗法应用最广泛的恶性肿瘤。由爱思唯尔公司出版
One of the major breakthroughs in oncology in the past decade has been the research and development of immune checkpoint inhibitors. Since the discovery of the PD-1/PD-L1 axis as a key mediator in peripheral self-tolerance and the subsequent discovery of its role promoting immune escape in cancers, the PD-1/PD-L1 pathway has produced considerable excitement from both a scientific and therapeutic standpoint. The past decade has seen an explosion in the number of clinical trials utilizing anti PD-1/PD-L1 therapy. Notably, pathologists have played a critical role in the development of these trials, and in guiding the use of anti PD-1/PD-L1 therapies in FDA-approved clinical settings. Analysis of tissue biopsies has been increasingly used to predict patients with which cancers are most likely to benefit from these new therapies. However, many open questions remain in a rapidly changing therapeutic and scientific landscape. In this review, we describe the basic functioning of the PD-1/PD-L1 axis in normal biology, how it is coopted by cancers to promote immune escape, and then review the literature regarding the prognostic value of tumoral PD-Ll expression on its own before discussing recent therapeutic advances, and the emerging role for pathologists in predicting response to anti PD-1/PD-L1 therapies. Special attention is given to melanoma and non small cell lung cancer, malignancies that have seen the broadest applications of anti PD-Ll/PD-1 therapies. Published by Elsevier Inc.