Mukherjee Malini, Mace Emily M, Carisey Alexandre F, Ahmed Nabil, Orange Jordan S
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77025, USA; Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77025, USA; Center for Human Immunobiology, Texas Children's Hospital, Houston, TX 77030, USA.
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77025, USA; Center for Human Immunobiology, Texas Children's Hospital, Houston, TX 77030, USA.
Mol Ther. 2017 Aug 2;25(8):1757-1768. doi: 10.1016/j.ymthe.2017.06.003. Epub 2017 Jun 26.
The lytic immunological synapse (IS) is a discrete structural entity formed after the ligation of specific activating receptors that leads to the destruction of a cancerous cell. The formation of an effector cell IS in cytotoxic T lymphocytes or natural killer cells is a hierarchical and stepwise rearrangement of structural and signaling components and targeted release of the contents of lytic granules. While recent advances in the generation and testing of cytotoxic lymphocytes expressing chimeric antigen receptors (CARs) has demonstrated their efficacy in the targeted lysis of tumor targets, the contribution and dynamics of IS components have not yet been extensively investigated in the context of engineered CAR cells. Understanding the biology of the CAR IS will be a powerful approach to efficiently guide the engineering of new CARs and help identify mechanistic problems in existing CARs. Here, we review the formation of the lytic IS and describe quantitative imaging-based measurements using multiple microscopy techniques at a single cell level that can be used in conjunction with established population-based assays to provide insight into the important cytotoxic function of CAR cells. The inclusion of this approach in the pipeline of CAR product design could be a novel and valuable innovation for the field.
溶细胞免疫突触（IS）是在特定激活受体连接后形成的离散结构实体，可导致癌细胞的破坏。细胞毒性T淋巴细胞或自然杀伤细胞中效应细胞IS的形成是结构和信号成分的分级和逐步重排以及溶细胞颗粒内容物的靶向释放。虽然表达嵌合抗原受体（CAR）的细胞毒性淋巴细胞的产生和测试方面的最新进展已证明它们在肿瘤靶标的靶向裂解中的功效，但在工程化CAR细胞的背景下，IS成分的贡献和动态尚未得到广泛研究。了解CAR IS的生物学特性将是有效指导新型CAR工程设计并帮助识别现有CAR中机制问题的有力方法。在这里，我们回顾溶细胞IS的形成，并描述在单细胞水平上使用多种显微镜技术进行的基于定量成像的测量，这些测量可与已建立的基于群体的检测方法结合使用，以深入了解CAR细胞的重要细胞毒性功能。将这种方法纳入CAR产品设计流程可能是该领域一项新颖且有价值的创新。
