Not All Immune Checkpoints Are Created Equal.
Not All Immune Checkpoints Are Created Equal.
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并非所有免疫检查点都是相等的。
DOI：
10.3389/fimmu.2018.01909
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发表时间：
2018
影响因子：
7.3
通讯作者：
Steinberger P
中科院分区：
文献类型：
--
作者：
De Sousa Linhares A;Leitner J;Grabmeier-Pfistershammer K;Steinberger P
通过免疫检查点CTLA-4和PD-1阻断T细胞抑制的抗体在过去15年中彻底改变了癌症治疗。T细胞表达额外的抑制性表面受体，这些受体被认为具有作为癌症免疫治疗靶点的潜力。目前正在临床上测试针对LAG-3和TIM-3的抗体，以评估其在患有晚期实体瘤或血液恶性肿瘤的患者中的有效性。此外，阻断人T细胞上的抑制性BTLA受体可能具有释放T细胞以有效对抗癌细胞的潜力。关于这些免疫检查点的许多研究都集中在小鼠模型上。对缺乏个体抑制性受体的动物的分析揭示了这些分子在调节T细胞以及一般免疫反应中的作用。目前有大量的努力来衡量靶向这些称为免疫检查点抑制剂的分子的抗体在癌症临床前模型中单独或以不同组合的疗效。小鼠和人类免疫学之间的差异保证了对人类免疫细胞的研究，以了解增强T细胞应答的各个途径的潜力。临床研究的结果不仅突出了免疫检查点抑制剂治疗癌症的巨大益处，而且还提供了关于其在调节T细胞和免疫系统其他细胞中作用的宝贵信息。然而，尽管CTLA-4和PD-1的临床相关性以及新兴免疫检查点的高潜力，但我们对这些分子生物学的理解仍存在重大差距，这可能会阻止其治疗潜力的充分实现。本文综述了PD-1，CTLA-4，BTLA，LAG-3和TIM-3，它们被认为是T细胞上表达的主要抑制性免疫检查点。它提供了我们目前对这些分子在调节T细胞反应中的作用的概念的总结，并讨论了我们知识中的主要模糊性和差距。我们强调，这些分子中的每一个都具有独特的性质，使其与其他分子区分开来。在旨在利用这些途径增强免疫反应以对抗癌症的治疗策略中应考虑它们独特的功能概况。
Antibodies that block T cell inhibition via the immune checkpoints CTLA-4 and PD-1 have revolutionized cancer therapy during the last 15 years. T cells express additional inhibitory surface receptors that are considered to have potential as targets in cancer immunotherapy. Antibodies against LAG-3 and TIM-3 are currently clinically tested to evaluate their effectiveness in patients suffering from advanced solid tumors or hematologic malignancies. In addition, blockade of the inhibitory BTLA receptors on human T cells may have potential to unleash T cells to effectively combat cancer cells. Much research on these immune checkpoints has focused on mouse models. The analysis of animals that lack individual inhibitory receptors has shed some light on the role of these molecules in regulating T cells, but also immune responses in general. There are current intensive efforts to gauge the efficacy of antibodies targeting these molecules called immune checkpoint inhibitors alone or in different combinations in preclinical models of cancer. Differences between mouse and human immunology warrant studies on human immune cells to appreciate the potential of individual pathways in enhancing T cell responses. Results from clinical studies are not only highlighting the great benefit of immune checkpoint inhibitors for treating cancer but also yield precious information on their role in regulating T cells and other cells of the immune system. However, despite the clinical relevance of CTLA-4 and PD-1 and the high potential of the emerging immune checkpoints, there are still substantial gaps in our understanding of the biology of these molecules, which might prevent the full realization of their therapeutic potential. This review addresses PD-1, CTLA-4, BTLA, LAG-3, and TIM-3, which are considered major inhibitory immune checkpoints expressed on T cells. It provides summaries of our current conception of the role of these molecules in regulating T cell responses, and discussions about major ambiguities and gaps in our knowledge. We emphasize that each of these molecules harbors unique properties that set it apart from the others. Their distinct functional profiles should be taken into account in therapeutic strategies that aim to exploit these pathways to enhance immune responses to combat cancer.
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DOI：
10.4049/jimmunol.0902490
发表时间：
2009-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cheung TC;Oborne LM;Steinberg MW;Macauley MG;Fukuyama S;Sanjo H;D'Souza C;Norris PS;Pfeffer K;Murphy KM;Kronenberg M;Spear PG;Ware CF
通讯作者：
Ware CF
影响因子：
4.4
作者：
Chemnitz, JM;Parry, RV;Riley, JL
通讯作者：
Riley, JL
DOI：
10.1084/jem.176.2.327
发表时间：
1992-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Baixeras E;Huard B;Miossec C;Jitsukawa S;Martin M;Hercend T;Auffray C;Triebel F;Piatier-Tonneau D
通讯作者：
Piatier-Tonneau D
影响因子：
30.5
作者：
Chiba, Shigeki;Baghdadi, Muhammad;Akiba, Hisaya;Yoshiyama, Hironori;Kinoshita, Ichiro;Dosaka-Akita, Hirotoshi;Fujioka, Yoichiro;Ohba, Yusuke;Gorman, Jacob V.;Colgan, John D.;Hirashima, Mitsuomi;Uede, Toshimitsu;Takaoka, Akinori;Yagita, Hideo;Jinushi, Masahisa
通讯作者：
Jinushi, Masahisa
影响因子：
15.9
作者：
Cohen, Cyrille J.;Gartner, Jared J.;Robbins, Paul F.
通讯作者：
Robbins, Paul F.