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

doi:10.1016/j.devcel.2022.01.002

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

Urology

Research output: Contribution to journal › Article › peer-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 language	English (US)
Pages (from-to)	329-343.e7
Journal	Developmental Cell
Volume	57
Issue number	3
DOIs	https://doi.org/10.1016/j.devcel.2022.01.002
State	Published - Feb 7 2022

Keywords

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

ASJC Scopus subject areas

Molecular Biology
General Biochemistry, Genetics and Molecular Biology
Developmental Biology
Cell Biology

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10.1016/j.devcel.2022.01.002

Cite this

Zhang, W., Zhong, W., Wang, B., Yang, J., Yang, J., Yu, Z., Qin, Z., Shi, A., Xu, W., Zheng, C., Schuchter, L. M., Karakousis, G. C., Mitchell, T. C., Amaravadi, R., Herlyn, M., Dong, H., Gimotty, P. A., Daaboul, G., Xu, X., & Guo, W. (2022). ICAM-1-mediated adhesion is a prerequisite for exosome-induced T cell suppression. Developmental Cell, 57(3), 329-343.e7. https://doi.org/10.1016/j.devcel.2022.01.002

Zhang, W, Zhong, W, Wang, B, Yang, J, Yang, J, Yu, Z, Qin, Z, Shi, A, Xu, W, Zheng, C, Schuchter, LM, Karakousis, GC, Mitchell, TC, Amaravadi, R, Herlyn, M, Dong, H, Gimotty, PA, Daaboul, G, Xu, X & Guo, W 2022, 'ICAM-1-mediated adhesion is a prerequisite for exosome-induced T cell suppression', Developmental Cell, vol. 57, no. 3, pp. 329-343.e7. https://doi.org/10.1016/j.devcel.2022.01.002

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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",

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doi = "10.1016/j.devcel.2022.01.002",

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AU - Zhang, Wei

AU - Zhong, Wenqun

AU - Wang, Beike

AU - Yang, Jiegang

AU - Yang, Jingbo

AU - Yu, Ziyan

AU - Qin, Zhiyuan

AU - Shi, Alex

AU - Xu, Wei

AU - Zheng, Cathy

AU - Schuchter, Lynn M.

AU - Karakousis, Giorgos C.

AU - Mitchell, Tara C.

AU - Amaravadi, Ravi

AU - Herlyn, Meenhard

AU - Dong, Haidong

AU - Gimotty, Phyllis A.

AU - Daaboul, George

AU - Xu, Xiaowei

AU - Guo, Wei

PY - 2022/2/7

Y1 - 2022/2/7

N2 - 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.

AB - 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.

KW - CD8 T cells

KW - ICAM-1

KW - PD-L1

KW - exosome

KW - extracellular vesicles

KW - immune suppression

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SP - 329-343.e7

JO - Developmental Cell

JF - Developmental Cell

IS - 3

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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