CAR T 细胞机械免疫学概览,Advanced Science

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CAR T 细胞机械免疫学概览
Advanced Science ( IF 14.3 ) Pub Date : 2020-11-03 , DOI: 10.1002/advs.202002628
Rui Li _{1,

2} , Chao Ma _{1,

2} , Haogang Cai _{3,

4} , Weiqiang Chen _{1,

2,

5}

Affiliation

嵌合抗原受体 (CAR) T 细胞转移是过继性 T 细胞免疫疗法的一种新范例。当与目标癌细胞接触时，CAR T 细胞与癌细胞形成非经典免疫突触，并动态协调多种关键力量来发挥细胞毒性免疫功能。这种免疫过程涉及 CAR 中的力传递和细胞骨架的时空重塑，以促进 CAR 激活和 CAR T 细胞的细胞毒功能。然而，对 CAR T 细胞和靶细胞之间界面的这种机械转导及其分子结构和信号传导的详细了解仍然不太明确，并且刚刚开始出现。本文总结了 CAR T 细胞机械免疫学的基本机制和原理，以及从正常细胞毒性 T 细胞免疫突触机械转导的研究中可以吸取的各种教训。还讨论了用于研究 CAR T 细胞机械免疫学的新型生物工程工具的最新发展和未来应用。相信这份进展报告将阐明 CAR T 细胞机械免疫学，并鼓励未来的研究揭示 CAR T 细胞免疫肿瘤学中较少探索但重要的机械传感和机械传导机制。

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The CAR T‐Cell Mechanoimmunology at a Glance

Chimeric antigen receptor (CAR) T‐cell transfer is a novel paradigm of adoptive T‐cell immunotherapy. When coming into contact with a target cancer cell, CAR T‐cell forms a nonclassical immunological synapse with the cancer cell and dynamically orchestrates multiple critical forces to commit cytotoxic immune function. Such an immunologic process involves a force transmission in the CAR and a spatiotemporal remodeling of cell cytoskeleton to facilitate CAR activation and CAR T‐cell cytotoxic function. Yet, the detailed understanding of such mechanotransduction at the interface between the CAR T‐cell and the target cell, as well as its molecular structure and signaling, remains less defined and is just beginning to emerge. This article summarizes the basic mechanisms and principles of CAR T‐cell mechanoimmunology, and various lessons that can be comparatively learned from interrogation of mechanotransduction at the immunological synapse in normal cytotoxic T‐cell. The recent development and future application of novel bioengineering tools for studying CAR T‐cell mechanoimmunology is also discussed. It is believed that this progress report will shed light on the CAR T‐cell mechanoimmunology and encourage future researches in revealing the less explored yet important mechanosensing and mechanotransductive mechanisms involved in CAR T‐cell immuno‐oncology.

更新日期：2020-12-16

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