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

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-y. 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.

Automated summary

This study reveals the co-localization of ICAM-1 and PD-L1 on exosomes, both of which are upregulated by interferon-y. The adhesion between TEVs and T cells mediated by ICAM-1-LFA-1 is crucial for exosomal PD-L1-mediated immune suppression.