The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation.
The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation.
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DOI：
10.3389/fimmu.2016.00550
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发表时间：
2016
影响因子：
7.3
通讯作者：
Boussiotis VA
中科院分区：
文献类型：
--
作者：
Bardhan K;Anagnostou T;Boussiotis VA
免疫系统维持一个严格组织的网络来防御外来粒子，同时避免自身反应。T淋巴细胞作为效应器，在协调免疫信号中起着重要的调节作用。尽管在胸腺选择过程中，中枢耐受机制导致大部分自身反应性T细胞被清除，但仍有一部分自身反应性淋巴细胞逃到外周，并对自身免疫构成威胁。免疫系统进化出各种机制来约束这些自身反应性T细胞并维持外周耐受性，包括T细胞能量、缺失和调节性T细胞（TRegs）的抑制。这些作用是由表达在T细胞及其配体上的刺激和抑制受体的复杂网络调节的，这些受体传递细胞间信号，指示T细胞遇到同源抗原的结果。在抑制性免疫介质中，由程序性细胞死亡1 （PD-1）受体（CD279）及其配体PD-L1 （B7-H1, CD274）和PD-L2 （B7-DC, CD273）组成的通路在诱导和维持外周耐受性以及维持T细胞的稳定性和完整性方面发挥重要作用。然而，PD-1:PD-L1/L2通路也介导了强有力的抑制信号，阻碍T效应细胞的增殖和功能，并对抗病毒和抗肿瘤免疫产生不利影响。靶向治疗这一途径已经成功地增强了T细胞对病毒病原体和肿瘤的免疫力。在这里，我们将简要概述PD-1通路组分的特性，PD-1参与调节的信号事件，以及它们对T效应细胞功能的影响。
The immune system maintains a critically organized network to defend against foreign particles, while evading self-reactivity simultaneously. T lymphocytes function as effectors and play an important regulatory role to orchestrate the immune signals. Although central tolerance mechanism results in the removal of the most of the autoreactive T cells during thymic selection, a fraction of self-reactive lymphocytes escapes to the periphery and pose a threat to cause autoimmunity. The immune system evolved various mechanisms to constrain such autoreactive T cells and maintain peripheral tolerance, including T cell anergy, deletion, and suppression by regulatory T cells (TRegs). These effects are regulated by a complex network of stimulatory and inhibitory receptors expressed on T cells and their ligands, which deliver cell-to-cell signals that dictate the outcome of T cell encountering with cognate antigens. Among the inhibitory immune mediators, the pathway consisting of the programed cell death 1 (PD-1) receptor (CD279) and its ligands PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273) plays an important role in the induction and maintenance of peripheral tolerance and for the maintenance of the stability and the integrity of T cells. However, the PD-1:PD-L1/L2 pathway also mediates potent inhibitory signals to hinder the proliferation and function of T effector cells and have inimical effects on antiviral and antitumor immunity. Therapeutic targeting of this pathway has resulted in successful enhancement of T cell immunity against viral pathogens and tumors. Here, we will provide a brief overview on the properties of the components of the PD-1 pathway, the signaling events regulated by PD-1 engagement, and their consequences on the function of T effector cells.
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影响因子：
15.3
作者：
Apostolou, I;von Boehmer, H
通讯作者：
von Boehmer, H
影响因子：
4.3
作者：
Appleman, Leonard J.;Chernova, Irene;Boussiotis, Vassiliki A.
通讯作者：
Boussiotis, Vassiliki A.
影响因子：
4.4
作者：
Blazar, BR;Carreno, BM;Taylor, PA
通讯作者：
Taylor, PA
影响因子：
30.5
作者：
Blackburn, Shawn D.;Shin, Haina;Haining, W. Nicholas;Zou, Tao;Workman, Creg J.;Polley, Antonio;Betts, Michael R.;Freeman, Gordon J.;Vignali, Dario A. A.;Wherry, E. John
通讯作者：
Wherry, E. John
DOI：
10.1056/nejmoa1200694
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brahmer JR;Tykodi SS;Chow LQ;Hwu WJ;Topalian SL;Hwu P;Drake CG;Camacho LH;Kauh J;Odunsi K;Pitot HC;Hamid O;Bhatia S;Martins R;Eaton K;Chen S;Salay TM;Alaparthy S;Grosso JF;Korman AJ;Parker SM;Agrawal S;Goldberg SM;Pardoll DM;Gupta A;Wigginton JM
通讯作者：
Wigginton JM