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Article

Immune Suppressive Effects of Plasma-Derived Exosome Populations in Head and Neck Cancer

by
Inga J. Beccard
1,
Linda Hofmann
1,
Jan C. Schroeder
1,
Sonja Ludwig
2,
Simon Laban
1,
Cornelia Brunner
1,
Ramin Lotfi
3,4,
Thomas K. Hoffmann
1,
Edwin K. Jackson
5,
Patrick J. Schuler
1,† and
Marie-Nicole Theodoraki
1,*,†
1
Department of Otorhinolaryngology, Head and Neck Surgery, University of Ulm, 89070 Ulm, Germany
2
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim, 68167 Mannheim, Germany
3
Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Services Baden-Württemberg-Hessen, 89081 Ulm, Germany
4
Institute for Transfusion Medicine, University Hospital Ulm, 89081 Ulm, Germany
5
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA
*
Author to whom correspondence should be addressed.
†
equal contribution.
Cancers 2020, 12(7), 1997; https://doi.org/10.3390/cancers12071997
Submission received: 2 July 2020 / Revised: 17 July 2020 / Accepted: 18 July 2020 / Published: 21 July 2020
(This article belongs to the Special Issue Advances in Head and Neck Squamous Cell Carcinoma (HNSCC))
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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 (Treg), 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 Treg 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.
Keywords: tumor-derived exosomes; immune regulation; HNSCC; liquid biopsy tumor-derived exosomes; immune regulation; HNSCC; liquid biopsy

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MDPI and ACS Style

Beccard, I.J.; Hofmann, L.; Schroeder, J.C.; Ludwig, S.; Laban, S.; Brunner, C.; Lotfi, R.; Hoffmann, T.K.; Jackson, E.K.; Schuler, P.J.; et al. Immune Suppressive Effects of Plasma-Derived Exosome Populations in Head and Neck Cancer. Cancers 2020, 12, 1997. https://doi.org/10.3390/cancers12071997

AMA Style

Beccard IJ, Hofmann L, Schroeder JC, Ludwig S, Laban S, Brunner C, Lotfi R, Hoffmann TK, Jackson EK, Schuler PJ, et al. Immune Suppressive Effects of Plasma-Derived Exosome Populations in Head and Neck Cancer. Cancers. 2020; 12(7):1997. https://doi.org/10.3390/cancers12071997

Chicago/Turabian Style

Beccard, Inga J., Linda Hofmann, Jan C. Schroeder, Sonja Ludwig, Simon Laban, Cornelia Brunner, Ramin Lotfi, Thomas K. Hoffmann, Edwin K. Jackson, Patrick J. Schuler, and et al. 2020. "Immune Suppressive Effects of Plasma-Derived Exosome Populations in Head and Neck Cancer" Cancers 12, no. 7: 1997. https://doi.org/10.3390/cancers12071997

APA Style

Beccard, I. J., Hofmann, L., Schroeder, J. C., Ludwig, S., Laban, S., Brunner, C., Lotfi, R., Hoffmann, T. K., Jackson, E. K., Schuler, P. J., & Theodoraki, M.-N. (2020). Immune Suppressive Effects of Plasma-Derived Exosome Populations in Head and Neck Cancer. Cancers, 12(7), 1997. https://doi.org/10.3390/cancers12071997

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