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

Circulating Exosomes Inhibit B Cell Proliferation and Activity

Department of Otorhinolaryngology and Head and Neck Surgery, Ulm University, 89075 Ulm, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Cancers 2020, 12(8), 2110; https://doi.org/10.3390/cancers12082110
Received: 23 June 2020 / Revised: 19 July 2020 / Accepted: 24 July 2020 / Published: 29 July 2020
(This article belongs to the Special Issue Advances in Head and Neck Squamous Cell Carcinoma (HNSCC))
(1) Background: Head and neck squamous cell carcinoma (HNSCC) is characterized by a distinctive suppression of the anti-tumor immunity, both locally in the tumor microenvironment (TME) and the periphery. Tumor-derived exosomes mediate this immune suppression by directly suppressing T effector function and by inducing differentiation of regulatory T cells. However, little is known about the effects of exosomes on B cells. (2) Methods: Peripheral B cells from healthy donors and HNSCC patients were isolated and checkpoint receptor expression was analyzed by flow cytometry. Circulating exosomes were isolated from the plasma of HNSCC patients (n = 21) and healthy individuals (n = 10) by mini size-exclusion chromatography. B cells from healthy individuals were co-cultured with isolated exosomes for up to 4 days. Proliferation, viability, surface expression of checkpoint receptors, and intracellular signaling were analyzed in B cells by flow cytometry. (3) Results: Expression of the checkpoint receptors PD-1 and LAG3 was increased on B cells from HNSCC patients. The protein concentration of circulating exosomes was increased in HNSCC patients as compared to healthy donors. Both exosomes from healthy individuals and HNSCC patients inhibited B cell proliferation and survival, in vitro. Surface expression of inhibitory and stimulatory checkpoint receptors on B cells was modulated in co-culture with exosomes. In addition, an inhibitory effect of exosomes on B cell receptor (BCR) signaling was demonstrated in B cells. (4) Conclusions: Plasma-derived exosomes show inhibitory effects on the function of healthy B cells. Interestingly, these inhibitory effects are similar between exosomes from healthy individuals and HNSCC patients, suggesting a physiological B cell inhibitory role of circulating exosomes. View Full-Text
Keywords: exosomes; B cells; Head and Neck Cancer; Bruton’s tyrosine kinase exosomes; B cells; Head and Neck Cancer; Bruton’s tyrosine kinase
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MDPI and ACS Style

Schroeder, J.C.; Puntigam, L.; Hofmann, L.; Jeske, S.S.; Beccard, I.J.; Doescher, J.; Laban, S.; Hoffmann, T.K.; Brunner, C.; Theodoraki, M.-N.; Schuler, P.J. Circulating Exosomes Inhibit B Cell Proliferation and Activity. Cancers 2020, 12, 2110. https://doi.org/10.3390/cancers12082110

AMA Style

Schroeder JC, Puntigam L, Hofmann L, Jeske SS, Beccard IJ, Doescher J, Laban S, Hoffmann TK, Brunner C, Theodoraki M-N, Schuler PJ. Circulating Exosomes Inhibit B Cell Proliferation and Activity. Cancers. 2020; 12(8):2110. https://doi.org/10.3390/cancers12082110

Chicago/Turabian Style

Schroeder, Jan C., Lisa Puntigam, Linda Hofmann, Sandra S. Jeske, Inga J. Beccard, Johannes Doescher, Simon Laban, Thomas K. Hoffmann, Cornelia Brunner, Marie-Nicole Theodoraki, and Patrick J. Schuler 2020. "Circulating Exosomes Inhibit B Cell Proliferation and Activity" Cancers 12, no. 8: 2110. https://doi.org/10.3390/cancers12082110

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