Beccard, Inga J. and Hofmann, Linda and Schroeder, Jan C. and Ludwig, Sonja and Laban, Simon and Brunner, Cornelia and Lotfi, Ramin and Hoffmann, Thomas K. and Jackson, Edwin K. and Schuler, Patrick J. and Theodoraki, Marie-Nicole
(2020)
Immune Suppressive Effects of Plasma-Derived Exosome Populations in Head and Neck Cancer.
Cancers, 12 (7).
p. 1997.
ISSN 2072-6694
Abstract
Plasma-derived exosomes of head and neck squamous cell carcinoma (HNSCC) patients carry inhibitory factors mediating immune suppression. Separation of tumor-derived exosomes (TEX) and non-TEX may assist in a better understanding of their respective parental cells. Here, we evaluate the impact of TEX or hematopoietic-derived exosomes on immune suppression. We evaluated apoptosis in CD8+ T cells, conversion of CD4+ T cells to regulatory T cells (T<sub>reg</sub>), and adenosine production by TEX, non-TEX, or total exosomes. Exosome protein cargo was significantly higher in total and CD45(−) exosomes from high stage compared to low stage patients. Furthermore, total and CD45(−) exosomes of high stage patients induced more apoptosis in CD8+ T cells than their low stage counterparts. CD69 suppression, a marker of reduced CD8+ T cell activation, was only mediated by CD45(−) exosomes. All fractions induced T<sub>reg</sub> differentiation, defined by CD39 expression, but only CD45(−) exosomes showed a stage-dependent conversion. CD45(−) exosomes produced higher adenosine concentrations than CD45(+) exosomes, concluding that adenosine production measured in total exosomes mainly derives from TEX. The presented results show significant induction of immune suppression by TEX in HNSCC. This immunosuppressive effect supports the potential role of exosomes as liquid biomarkers for disease stage and level of immune suppression.
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Details
| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Beccard, Inga J. | | | | | Hofmann, Linda | | | | | Schroeder, Jan C. | | | | | Ludwig, Sonja | | | | | Laban, Simon | | | | | Brunner, Cornelia | | | | | Lotfi, Ramin | | | | | Hoffmann, Thomas K. | | | | | Jackson, Edwin K. | edj@pitt.edu | edj | | | Schuler, Patrick J. | | | | | Theodoraki, Marie-Nicole | | | |
|
| Date: |
21 July 2020 |
| Date Type: |
Publication |
| Journal or Publication Title: |
Cancers |
| Volume: |
12 |
| Number: |
7 |
| Publisher: |
MDPI AG |
| Page Range: |
p. 1997 |
| DOI or Unique Handle: |
10.3390/cancers12071997 |
| Schools and Programs: |
School of Medicine > Pharmacology and Chemical Biology |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
tumor-derived exosomes, immune regulation, HNSCC, liquid biopsy |
| ISSN: |
2072-6694 |
| Official URL: |
http://dx.doi.org/10.3390/cancers12071997 |
| Funders: |
Foundation for Head and Neck Tumor research |
| Article Type: |
Research Article |
| Date Deposited: |
01 Jul 2021 14:28 |
| Last Modified: |
01 Jul 2021 14:28 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/41295 |
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