Antagonists of PD-1 and PD-L1 in Cancer Treatment.
Antagonists of PD-1 and PD-L1 in Cancer Treatment.
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DOI：
10.1053/j.seminoncol.2015.05.013
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发表时间：
2015-08
影响因子：
4
通讯作者：
Topalian SL
中科院分区：
文献类型：
--
作者：
Lipson EJ;Forde PM;Hammers HJ;Emens LA;Taube JM;Topalian SL
PD-1通路包括免疫细胞共受体程序性死亡1（PD-1）及其配体PD-L1（B7-H1）和PD-L2（B7-DC），介导肿瘤微环境中的局部免疫抑制。设计用于阻断PD-1或PD-L1的药物“释放抗肿瘤免疫的刹车”，并在几种类型的晚期癌症中表现出临床活性，验证了该途径作为癌症治疗靶点的作用。两种这样的药物最近已被批准用于治疗难治性晚期黑色素瘤，预计监管机构将批准用于其他癌症类型的一线和二线治疗。PD-1/PD-L1阻断药物可管理的安全性特征表明它们适合门诊给药和联合治疗的开发。正在进行的研究旨在确定生物标志物以指导患者选择，这将进一步改善这些药物的风险：效益比。
The PD-1 pathway, comprising the immune cell co-receptor Programmed Death 1 (PD-1) and its ligands, PD-L1 (B7-H1) and PD-L2 (B7-DC), mediates local immunosuppression in the tumor microenvironment. Drugs designed to block PD-1 or PD-L1 “release the brakes” on anti-tumor immunity and have demonstrated clinical activity in several types of advanced cancers, validating this pathway as a target for cancer therapy. Two such drugs have recently been approved to treat refractory advanced melanoma, and regulatory approvals in first- and second-line settings for additional cancer types are anticipated. The manageable safety profile of PD-1/PD-L1 blocking drugs identifies them as suitable for outpatient administration and the development of combinatorial therapies. Ongoing studies aim to identify biomarkers to guide patient selection, which would further improve the risk:benefit ratio for these drugs.