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

Rashid,Mohammad H.; Borin,Thaiz F.; Ara,Roxan; Piranlioglu,Raziye; Achyut,Bhagelu R.; Korkaya,Hasan; Liu,Yutao; Arbab,Ali S.

doi:10.3892/or.2021.7936

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

Authors:
- Mohammad H. Rashid
- Thaiz F. Borin
- Roxan Ara
- Raziye Piranlioglu
- Bhagelu R. Achyut
- Hasan Korkaya
- Yutao Liu
- Ali S. Arbab
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Affiliations: Laboratory of Tumor Angiogenesis, Georgia Cancer Center, Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USA, Cancer Animal Models Shared Resource, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA, Molecular Oncology and Biomarkers Program, Georgia Cancer Center, Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USA, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
Published online on: January 14, 2021 https://doi.org/10.3892/or.2021.7936
Pages: 1171-1181
Copyright: © Rashid et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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