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

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;
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.

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.

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.

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