Boothby Mark
Department of Pathology, Microbiology & Immunology, Vanderbilt University, Nashville, TN, USA.
F1000Res. 2016 Feb 18;5. doi: 10.12688/f1000research.7027.1. eCollection 2016.
The excitement surrounding checkpoint inhibitors in the treatment of patients with cancer exemplifies a triumph of the long-term value of investing in basic science and fundamental questions of T-cell signaling. The pharmaceutical future actively embraces ways of making more patients' cancers responsive to these inhibitors. Such a process will be aided by elucidation of signaling and regulation. With thousands of articles spread across almost 30 years, this commentary can touch only on portions of the canonical picture of T-cell signaling and provide a few parables from work on mammalian (or mechanistic) target of rapamycin (mTOR) pathways as they link to early and later phases of lymphocyte activation. The piece will turn a critical eye to some issues with models about these pathways in T cells. Many of the best insights lie in the future despite all that is uncovered already, but a contention is that further therapeutic successes will be fostered by dealing with disparities among findings and attention to the temporal, spatial, and stochastic aspects of T-cell responses. Finally, thoughts on some (though not all) items urgently needed for future progress will be mooted.
围绕检查点抑制剂治疗癌症患者的兴奋之情体现了投资基础科学和T细胞信号传导基本问题的长期价值所取得的胜利。制药业的未来积极探索让更多患者的癌症对这些抑制剂产生反应的方法。阐明信号传导和调节将有助于这一过程。在近30年里有数千篇文章，本评论只能触及T细胞信号传导经典图景的一部分，并提供一些关于雷帕霉素哺乳动物（或机制）靶点（mTOR）通路的研究实例，因为它们与淋巴细胞激活的早期和后期阶段相关。本文将批判性地审视T细胞中这些通路模型的一些问题。尽管已经揭示了很多，但许多最佳见解仍在未来，但有一种观点认为，通过处理研究结果之间的差异以及关注T细胞反应的时间、空间和随机方面，将促进进一步的治疗成功。最后，将讨论一些（尽管不是全部）未来进展迫切需要的事项。
