微泡
细胞生物学
生物
细胞间粘附分子-1
细胞毒性T细胞
细胞外
CD8型
细胞粘附
细胞粘附分子
外体
细胞间粘附分子
下调和上调
免疫系统
ICAM-1
细胞
免疫学
生物化学
体外
小RNA
基因
作者
Wei Zhang,Wen-Qun Zhong,Beike Wang,Jiegang Yang,Zi-yan Yu,Zhiyuan Qin,Alex Y. Shi,Wei Xu,Cathy Zheng,Lynn M. Schuchter,Giorgos C. Karakousis,Tara C. Mitchell,Ravi K. Amaravadi,Meenhard Herlyn,Haidong Dong,Phyllis A. Gimotty,George G. Daaboul,Xiaowei Xu,Wei Guo
标识
DOI:10.1016/j.devcel.2022.01.002
摘要
Tumor-derived extracellular vesicles (TEVs) suppress the proliferation and cytotoxicity of CD8+ T cells, thereby contributing to tumor immune evasion. Here, we report that the adhesion molecule intercellular adhesion molecule 1 (ICAM-1) co-localizes with programmed death ligand 1 (PD-L1) on the exosomes; both ICAM-1 and PD-L1 are upregulated by interferon-γ. Exosomal ICAM-1 interacts with LFA-1, which is upregulated in activated T cells. Blocking ICAM-1 on TEVs reduces the interaction of TEVs with CD8+ T cells and attenuates PD-L1-mediated suppressive effects of TEVs. During this study, we have established an extracellular vesicle-target cell interaction detection through SorTagging (ETIDS) system to assess the interaction between a TEV ligand and its target cell receptor. Using this system, we demonstrate that the interaction of TEV PD-L1 with programmed cell death 1 (PD-1) on T cells is significantly reduced in the absence of ICAM-1. Our study demonstrates that ICAM-1-LFA-1-mediated adhesion between TEVs and T cells is a prerequisite for exosomal PD-L1-mediated immune suppression.
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