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. [ABSTRACT FROM AUTHOR]