@article{e1e0d7631f0d4a2c92fc4899f5a5d55f,
title = "ICAM-1-mediated adhesion is a prerequisite for exosome-induced T cell suppression",
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.",
keywords = "CD8 T cells, ICAM-1, PD-L1, exosome, extracellular vesicles, immune suppression",
author = "Wei Zhang and Wenqun Zhong and Beike Wang and Jiegang Yang and Jingbo Yang and Ziyan Yu and Zhiyuan Qin and Alex Shi and Wei Xu and Cathy Zheng and Schuchter, {Lynn M.} and Karakousis, {Giorgos C.} and Mitchell, {Tara C.} and Ravi Amaravadi and Meenhard Herlyn and Haidong Dong and Gimotty, {Phyllis A.} and George Daaboul and Xiaowei Xu and Wei Guo",
note = "Funding Information: We thank Dr. Changsong Yang for his help with electron microscopy and Dr. Shiaw-Yih Lin (MD Anderson Cancer Center) for the colon cancer cell line HCT116. This work was supported by NIH R35 GM141832 to W.G. and NCI CA174523 ( SPORE ) grant to M.H., L.M.S., R.A., T.C.M., W.G., X.X., G.C.K., and P.A.G. Funding Information: We thank Dr. Changsong Yang for his help with electron microscopy and Dr. Shiaw-Yih Lin (MD Anderson Cancer Center) for the colon cancer cell line HCT116. This work was supported by NIH R35 GM141832 to W.G. and NCI CA174523 (SPORE) grant to M.H. L.M.S. R.A. T.C.M. W.G. X.X. G.C.K. and P.A.G. W. Zhang and W.G. conceived the project and designed the experiments. W. Zhang, W. Zhong, B.W. and Jiegang Yang purified and characterized extracellular vesicles. W. Zhang, W. Zhong, B.W. Jiegang Yang, Jingbo Yang, and Z.Y. performed the mice experiments. W. Zhang and W. Zhong established the knockdown and knockout cell lines, collected exosomes, and performed the T cell binding assays and T cell proliferation and activation assays. W. Zhang, W. Zhong, and Z.Q. performed ELISA assays. W. Zhang, W. Zhong, and B.W. performed the nanoparticle tracking analysis. W. Zhang, W. Zhong, B.W. Jiegang Yang, and A.S. performed the immunoprecipitation and western blot analysis. W. Zhang established the EDITS system and tested the exosomal PD-L1/PD-1 interaction. W. Zhong performed immune-TEM and ICAM-1+ exosome depletion assays. W. Zhang, W. Zhong, and Jingpo Yang performed the flow cytometry experiments. X.X. performed pathological analyses. W.X. C.Z. L.M.S. G.C.K. T.C.M. and R.A. provided human samples and associated clinical data. M.H. and H.D. provided antibodies and cell lines. W. Zhang, W. Zhong, B.W. and Jiegang Yang analyzed and interpreted the data. W. Zhang and P.A.G. performed the statistical analysis. W. Zhang, W. Zhong, and W.G. wrote the paper. A.S. W.X. R.A. and X.X. edited the paper. All authors have read and approved the final manuscript. G.D. is an employee and shareholder of NanoView Biosciences Inc. We worked to ensure ethnic or other types of diversity in the recruitment of human subjects. We worked to ensure diversity in experimental samples through the selection of the cell lines. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = feb,
day = "7",
doi = "10.1016/j.devcel.2022.01.002",
language = "English (US)",
volume = "57",
pages = "329--343.e7",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "3",
}