CAR-T细胞突触的物质景观。
The physical landscape of CAR-T synapse.
发表日期：2023 Sep 14
作者：
Yiwei Xiong, Kendra A Libby, Xiaolei Su
来源：
Cellular & Molecular Immunology
摘要：
嵌合抗原受体（CAR）-T细胞与其癌细胞靶标形成动态的免疫突触。在CAR-抗原结合后，CAR-T突触形成、成熟，最终解离，伴随着细胞表面蛋白、脂质和糖类的大规模重塑。在本综述中，我们提供了理解CAR-T突触蛋白质分布、膜拓扑及力传递的视角。我们强调CAR-T突触与T细胞受体（TCR）突触的差异特征，包括无序的蛋白质模式、可调节的突触宽度、多样的力学响应属性及由此产生的信号传递后果。通过一系列例子，我们阐述了揭示CAR-T突触的生物物理特性如何指导设计具有改进抗肿瘤功能的CAR-T细胞。版权所有©2023生物物理学会。由Elsevier Inc.发行，保留所有权利。
Chimeric antigen receptor (CAR)-T cells form dynamic immunological synapses with their cancer cell targets. Following a CAR-antigen engagement, the CAR-T synapse forms, matures, and finally disassembles, accompanied by substantial remodeling of cell surface proteins, lipids, and glycans. In this review, we provide perspectives for understanding protein distribution, membrane topology, and force transmission across the CAR-T synapse. We highlight the features of CAR-T synapses that differ from T cell receptor (TCR) synapses, including the disorganized protein pattern, adjustable synapse width, and diverse mechano-responding properties and the resulting signaling consequences. Through a range of examples, we illustrate how revealing the biophysical nature of the CAR-T synapse could guide the design of CAR-Ts with improved anti-tumor function.Copyright © 2023 Biophysical Society. Published by Elsevier Inc. All rights reserved.