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

Wei Zhang, Wenqun Zhong, Beike Wang, Jiegang Yang, Jingbo Yang, Ziyan Yu, Zhiyuan Qin, Alex Shi, Wei Xu, Cathy Zheng, Lynn M. Schuchter, Giorgos C. Karakousis, Tara C. Mitchell, Ravi Amaravadi, Meenhard Herlyn, Haidong Dong, Phyllis A. Gimotty, George Daaboul, Xiaowei Xu, Wei Guo

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)329-343.e7
JournalDevelopmental Cell
Volume57
Issue number3
DOIs
StatePublished - Feb 7 2022

Keywords

  • CD8 T cells
  • exosome
  • extracellular vesicles
  • ICAM-1
  • immune suppression
  • PD-L1

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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