Lipson Evan J, Forde Patrick M, Hammers Hans-Joerg, Emens Leisha A, Taube Janis M, Topalian Suzanne L
Department of Oncology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.
Department of Oncology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Department of Dermatology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Department of Pathology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.
Semin Oncol. 2015 Aug;42(4):587-600. doi: 10.1053/j.seminoncol.2015.05.013. Epub 2015 Jun 10.
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 melanoma and lung cancers, 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.
程序性死亡蛋白1（PD-1）通路由免疫细胞共受体程序性死亡蛋白1及其配体程序性死亡配体1（PD-L1，B7-H1）和程序性死亡配体2（PD-L2，B7-DC）组成，介导肿瘤微环境中的局部免疫抑制。旨在阻断PD-1或PD-L1的药物“松开”了抗肿瘤免疫的“刹车”，并已在多种类型的晚期癌症中显示出临床活性，证实该通路可作为癌症治疗的靶点。最近有两种此类药物已被批准用于治疗黑色素瘤和肺癌，预计还会有更多癌症类型在一线和二线治疗中获得监管批准。PD-1/PD-L1阻断药物可控的安全性表明它们适合门诊给药以及联合疗法的开发。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。
