Manipulating the TCR signaling network for cellular immunotherapy: Challenges & opportunities.
Manipulating the TCR signaling network for cellular immunotherapy: Challenges & opportunities.
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DOI：
10.1016/j.molimm.2020.04.007
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发表时间：
2020-07
影响因子：
3.6
通讯作者：
Singh NJ
中科院分区：
文献类型：
--
作者：
Matson CA;Singh NJ
T细胞可以通过消除感染和肿瘤来帮助赋予保护性免疫力，或者通过破坏宿主细胞来驱动免疫病理学。这两种结果都需要一系列步骤，从幼稚T细胞的激活到它们的克隆扩增，分化和迁移到组织部位。除了通过T细胞受体（TCR）特异性识别抗原外，来自共刺激分子、细胞因子和代谢物的多种辅助信号也影响T细胞应答进展的沿着每一步。目前在许多临床背景下修饰效应T细胞功能的努力集中在后者-其包括抗原非依赖性和广泛的背景调节剂。毫不奇怪，这种方法通常伴随着不良事件，因为它们也影响与特定治疗无关的T细胞。相比之下，通过精确靶向抗原特异性TCR信号来微调T细胞应答具有以集中的方式从根本上改变治疗策略的潜力。然而，这种方法的发展，需要更好地了解TCR的功能和生化信号网络耦合到它。在这篇文章中，我们回顾了一些最近的进展，突出了重要的作用，TCR信号在整个活化和分化的T细胞在免疫反应。我们讨论了如何，升值的特定信号传导方式和变体配体的影响TCR的功能有可能影响下一代的药理学和细胞疗法的设计原则，特别是在涉及过继细胞转移的肿瘤免疫治疗的背景下。
T cells can help confer protective immunity by eliminating infections and tumors or drive immunopathology by damaging host cells. Both outcomes require a series of steps from the activation of naïve T cells to their clonal expansion, differentiation and migration to tissue sites. In addition to specific recognition of the antigen via the T cell receptor (TCR), multiple accessory signals from costimulatory molecules, cytokines and metabolites also influence each step along the progression of the T cell response. Current efforts to modify effector T cell function in many clinical contexts focus on the latter – which encompass antigen-independent and broad, contextual regulators. Not surprisingly, such approaches are often accompanied by adverse events, as they also affect T cells not relevant to the specific treatment. In contrast, fine tuning T cell responses by precisely targeting antigen-specific TCR signals has the potential to radically alter therapeutic strategies in a focused manner. Development of such approaches, however, requires a better understanding of functioning of the TCR and the biochemical signaling network coupled to it. In this article, we review some of the recent advances which highlight important roles of TCR signals throughout the activation and differentiation of T cells during an immune response. We discuss how, an appreciation of specific signaling modalities and variant ligands that influence the function of the TCR has the potential to influence design principles for the next generation of pharmacologic and cellular therapies, especially in the context of tumor immunotherapies involving adoptive cell transfers.
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影响因子：
4.4
作者：
Chemnitz, JM;Parry, RV;Riley, JL
通讯作者：
Riley, JL
影响因子：
30.5
作者：
Chang CH;Pearce EL
通讯作者：
Pearce EL
影响因子：
7
作者：
Curtsinger JM;Mescher MF
通讯作者：
Mescher MF
DOI：
10.1084/jem.20001021
发表时间：
2002-03-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Blattman JN;Antia R;Sourdive DJ;Wang X;Kaech SM;Murali-Krishna K;Altman JD;Ahmed R
通讯作者：
Ahmed R
影响因子：
64.8
作者：
Daniels, Mark A.;Teixeiro, Emma;Palmer, Ed
通讯作者：
Palmer, Ed