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Author Notes:

Dr Ali S. Arbab, Laboratory of Tumor Angiogenesis, Georgia Cancer Center, Department of Biochemistry and Molecular Biology, Augusta University, 1410 Laney Walker Blvd., Room CN 3315, Augusta, GA 30912, USA, E-mail: aarbab@augusta .edu

MHR conceived the hypothesis, designed and performed the experiments, and conducted the data collection, data analysis, and interpretation, and wrote the manuscript. TFB conducted acquisition of the in vitro data and edited the manuscript. RA performed the animal experiments and treated the animals. RP conducted the data interpretation and edited the manuscript. BRA helped with planning the in vitro T-cell experiments. HK guided MDSC collection and types, and helped with implantation of breast cancers. YL provided laboratory facilities for NTA, data interpretation, and editing of the manuscript. ASA supervised the findings of this work, aided in interpreting the results, and provided the funds and critical revision of the manuscript.

The authors thank Dr Rhea-Beth Markowitz, Director, Office of Grant Development, Georgia Cancer Center for help with the English language editing of the manuscript.

The authors have declared that no competing interest exists.

Subjects:

Research Funding:

This study was supported by the Georgia Cancer Center Startup Fund and Intramural Grant Program at Augusta University (Augusta, GA, USA) to ASA.

Keywords:

  • exosomes
  • myeloid-derived suppressor cells
  • tumor microenvironment
  • CD8 T cells
  • activation-induced cell death
  • Animals
  • CD8-Positive T-Lymphocytes
  • Cell Communication
  • Cell Line, Tumor
  • Disease Models, Animal
  • Exosomes
  • Humans
  • Macrophages
  • Mice
  • Myeloid-Derived Suppressor Cells
  • Neoplasms
  • Primary Cell Culture
  • Tumor Escape
  • Tumor Microenvironment

Critical immunosuppressive effect of MDSC-derived exosomes in the tumor microenvironment

Tools:

Journal Title:

Oncology Reports

Volume:

Volume 45, Number 3

Publisher:

, Pages 1171-1181

Type of Work:

Article | Final Publisher PDF

Abstract:

Myeloid-derived suppressor cells (MDSCs) are an indispensable component of the tumor microenvironment (TME). Along with the role of MDSC immunosuppression and antitumor immunity, MDSCs facilitate tumor growth, differentiation, and metastasis in several ways that are yet to be explored. Like any other cell type, MDSCs also release a tremendous number of exosomes, or nanovesicles of endosomal origin, that participate in intercellular communications by dispatching biological macromolecules. There have been no investigational studies conducted to characterize the role of MDSC-derived exosomes (MDSC exo) in modulating the TME. In this study, we isolated MDSC exo and demonstrated that they carry a significant level of proteins that play an indispensable role in tumor growth, invasion, angiogenesis, and immunomodulation. We observed a higher yield and more substantial immunosuppressive potential of exosomes isolated from MDSCs in the primary tumor area than those in the spleen or bone marrow. Our in vitro data suggest that MDSC exo are capable of hyper-activating or exhausting CD8 T-cells and induce reactive oxygen species production that elicits activation-induced cell death. We confirmed the depletion of CD8 T-cells in vivo by treating mice with MDSC exo. We also observed a reduction in pro-inflammatory M1-macrophages in the spleen of those animals. Our results indicate that the immunosuppressive and tumor-promoting functions of MDSCs are also implemented by MDSC-derived exosomes which would open up a new avenue of MDSC research and MDSC-targeted therapy.

Copyright information:

© Rashid et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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