ICAM-1-mediated adhesion is a prerequisite for exosome-induced T cell suppression

• Published in: Developmental cell Vol. 57; no. 3; pp. 329 - 343.e7
• Main Authors: Zhang, Wei, Zhong, Wenqun, Wang, Beike, Yang, Jiegang, Yang, Jingbo, Yu, Ziyan, Qin, Zhiyuan, Shi, Alex, Xu, Wei, Zheng, Cathy, Schuchter, Lynn M., Karakousis, Giorgos C., Mitchell, Tara C., Amaravadi, Ravi, Herlyn, Meenhard, Dong, Haidong, Gimotty, Phyllis A., Daaboul, George, Xu, Xiaowei, Guo, Wei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.02.2022
• Subjects: Animals; B7-H1 Antigen - metabolism; CD8+ T cells; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cell Adhesion - drug effects; Cell Communication - drug effects; Cell Line, Tumor; Disease Models, Animal; exosome; Exosomes - drug effects; Exosomes - metabolism; Exosomes - ultrastructure; extracellular vesicles; ICAM-1; immune suppression; Immunosuppression Therapy; Intercellular Adhesion Molecule-1 - metabolism; Interferon-gamma - pharmacology; Melanoma - pathology; Mice; Mice, Inbred C57BL; Neoplasm Proteins - metabolism; PD-L1; Protein Binding - drug effects; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Up-Regulation - drug effects; PD-L1; CD8+ T cells; ICAM-1; extracellular vesicles; immune suppression; exosome; CD8(+) T cells
• ISSN: 1534-5807; 1878-1551; 1878-1551
• DOI: 10.1016/j.devcel.2022.01.002

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. [Display omitted] •ICAM-1 and PD-L1 co-localize on exosomes and are both upregulated by interferon-γ•ICAM-1 is a prerequisite for exosomal PD-L1-mediated inhibition of CD8+ T cells•Reciprocal upregulation of ICAM-1 and LFA-1 promotes exosome-T cell interaction•Established an assay system for the interaction of exosomal PD-L1 with PD-1 on T cells Tumor-derived exosomes can suppress the proliferation and cytotoxicity of CD8+ T cells. Zhang and colleagues report that the exosomes adhere to activated CD8 T cells through an ICAM-1-LFA-1 interaction, which is a prerequisite for exosomal PD-L1-PD-1 binding and T cell suppression.