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PD-1检查点通路的分子和生化特征
Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway


Vassiliki A. Boussiotis ... 肿瘤 • 2016.11.03
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从分子机制到联合治疗:探讨提高PD-1肿瘤免疫治疗效果的新策略

 

卜夏

河南大学肿瘤中心,河南大学第一附属医院肿瘤科

 

Vassiliki Boussiotis发表在《新英格兰医学杂志》的综述“PD-1免疫检查点通路的分子和生化特征”1,全面论述了PD-1/PD-L1分子和结构特点,抑制T细胞功能的分子机制和信号转导途径,PD-L1在肿瘤细胞表达的调控机制,PD-1在T细胞激活和耗竭状态下物质代谢调控中的作用等。这些论述和观点,对探讨PD-1肿瘤免疫治疗的分子机制,选择合理的PD-1单抗或PD-L1单抗联合治疗药物治疗恶性肿瘤提供了全面系统的科学依据。

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由细胞程序性死亡受体1(PD-1;也称为CD279)及其配体PD-L1(B7-H1或CD274)、PD-L2(B7-DC或CD273)组成的通路,在维持外周免疫耐受(即维持自身反应性T细胞静止的机制,这些T细胞已经成熟并且在胸腺中发育时从中枢免疫耐受机制逃脱)中起着至关重要的作用。肿瘤和引起慢性感染的病原体能利用该途径从T细胞介导的肿瘤特异性和病原体特异性免疫中逃逸。以PD-1及其配体为靶向的抗体疗法已经在多种癌症中显示出显著的缓解率,它们和以CTLA-4为靶向的抗体一起彻底改变了癌症治疗(本综述中所用蛋白质缩写的列表见补充附录,其与本文全文均可在NEJM.org获取)。除了临床取得的成功,目前持续进行的工作还发现了PD-1靶向作用的分子机制。在这里,我对受PD-1(与配体)结合调控的分子和生化事件以及它们对决定T细胞命运和功能的细胞内、外机制所产生的影响进行简要综述。





作者信息

Vassiliki A. Boussiotis, M.D., Ph.D.
From the Division of Hematology–Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston. Address reprint requests to Dr. Boussiotis at Beth Israel Deaconess Medical Center, 330 Brookline Ave., Dana 513, Boston MA 02215, or at vboussio@bidmc.harvard.edu.

 

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