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Medientyp:
E-Artikel
Titel:
Circulating Exosomes Inhibit B Cell Proliferation and Activity
Beteiligte:
Schroeder, Jan C.;
Puntigam, Lisa;
Hofmann, Linda;
Jeske, Sandra S.;
Beccard, Inga J.;
Doescher, Johannes;
Laban, Simon;
Hoffmann, Thomas K.;
Brunner, Cornelia;
Theodoraki, Marie-Nicole;
Schuler, Patrick J.
Erschienen:
MDPI AG, 2020
Erschienen in:
Cancers, 12 (2020) 8, Seite 2110
Sprache:
Englisch
DOI:
10.3390/cancers12082110
ISSN:
2072-6694
Entstehung:
Anmerkungen:
Beschreibung:
(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.