PD-1 targeting in cancer immunotherapy.
PD-1 targeting in cancer immunotherapy.
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DOI：
10.1002/cncr.27832
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发表时间：
2013-12-01
期刊：
影响因子：
6.2
通讯作者：
Ferris, Robert
中科院分区：
文献类型：
--
作者：
Ferris, Robert
癌症免疫治疗一直受到复杂、笨重的试剂和细胞、个性化和费力的准备以及临床疗效可疑的阻碍。最近关于一类新的单抗(MoAbs)的报道引起了人们对该领域的极大热情，这是基于传递给适应性免疫系统的抑制信号的中断以及在现有系统免疫治疗的背景下临床疗效的展示。这些“检查点”受体抑制剂，如抗程序性细胞死亡蛋白1(PD-1/PD-L1)，阻断了多种癌症T细胞上的抑制性受体信号，为这一新兴癌症治疗方法的加速发展开辟了广阔的前景。肿瘤浸润性淋巴细胞(TILs)是肿瘤微环境(TME)内对肿瘤相关抗原(TA)动态宿主免疫反应的主要效应细胞。然而，TME构成了一个潜在的敌对环境，可能会导致T细胞功能障碍，以避免免疫细胞攻击，从而允许肿瘤进展。2肿瘤抑制TIL的机制之一涉及受体-配体相互作用，其中杀伤细胞的活性由PD-1等免疫检查点抑制受体产生的抑制信号决定。T细胞抑制受体家族3-7通过负性调节免疫细胞(如T细胞和自然杀伤细胞)中的信号，包括T细胞受体(TCR)介导的激活信号来限制T细胞的功能。8我们对翻译肿瘤免疫学的新理解表明，可以使用单抗来阻断这些抑制性受体，包括抗细胞毒T淋巴细胞抗原-4(CTLA-4)(以美国食品和药物管理局新批准的单抗ipilimumab为靶标)，以及最近报道的阻断PD-1途径的单抗。9、10研究表明，这种T细胞功能损害可以通过阻断这些抑制性受体来恢复，5-7导致了最近观察到的临床疗效。
Cancer immunotherapy has been hampered by complex, cumbersome agents and cells; individualized and laborious preparations; and questionable clinical efficacy. Recent reports of a new class of monoclonal antibodies (MoAbs) have garnered tremendous enthusiasm for the field, based on the interruption of suppressive signals that are delivered to the adaptive immune system and the demonstration of clinical efficacy within the setting of off-the-shelf systemic immunotherapy. These" checkpoint" receptor inhibitors such as anti-programmed cell death protein 1 (PD-1/PD-L1) block inhibitory receptor signaling in T cells from a variety of cancers and widen the vista for the accelerated development of this emerging modality of cancer therapy.Tumor-infiltrating lymphocytes (TILs) are major effector cells in the dynamic host immune responses to tumor-associated antigens (TAs) within the tumor microenvironment (TME). 1 However, the TME constitutes a potentially hostile milieu, which may induce T-cell dysfunction to avoid immune cell attack, thus permitting tumor progression. 2 One of the mechanisms of tumor-induced inhibition of TILs involves a receptor-ligand interaction in which cytolytic activity is determined by inhibitory signaling generated by immune checkpoint inhibitory receptors such as PD-1. The family of T-cell inhibitory receptors3–7 limits T-cell functions by negatively regulating signals in immune cells (eg, T cells and natural killer cells), including activating signals mediated by the T cell receptor (TCR). 8 Our emerging understanding of translational tumor immunology has indicated that effective antitumor immunity can be achieved using MoAbs to block these inhibitory receptors, including anticytotoxic T lymphocyte antigen-4 (CTLA-4)(targeted by the MoAb ipilimumab, which has been newly approved by the US Food and Drug Administration), as well as the recently reported PD-1 pathway-blocking MoAb. 9, 10 Studies have demonstrated that this T-cell functional impairment can be restored through the blockade of these inhibitory receptors, 5–7 leading to the clinical efficacy that has been observed recently.
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DOI：
10.4049/jimmunol.1001157
发表时间：
2010-12-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Vazquez-Cintron EJ;Monu NR;Frey AB
通讯作者：
Frey AB
影响因子：
15.9
作者：
Baitsch, Lukas;Baumgaertner, Petra;Speiser, Daniel E.
通讯作者：
Speiser, Daniel E.
DOI：
10.1084/jem.20100643
发表时间：
2010-09-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Sakuishi K;Apetoh L;Sullivan JM;Blazar BR;Kuchroo VK;Anderson AC
通讯作者：
Anderson AC
影响因子：
6.5
作者：
Chapon, Maxime;Randriamampita, Clotilde;Bercovici, Nadege
通讯作者：
Bercovici, Nadege
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