期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 22, 页码 -出版社
MDPI
DOI: 10.3390/ijms232214446
关键词
tumor-derived exosomes; HNSCC; exosomes; extracellular vesicles; B cells; regulatory B cells; ATP; adenosine; immunomodulation; apoptosis
资金
- Special program to promote young talents in clinical research, University of Basel [DMS23349]
- Cancer League Basel [18/2016]
This study investigated the effects of tumor-derived exosomes (TEX) on B cells in the presence of ATP. The results showed that TEX exhibited immunosuppressive effects by inhibiting B-cell proliferation and immunostimulatory effects by downregulating CD39 expression. Furthermore, TEX were able to modulate the expression of apoptosis-associated proteins.
Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy. Tumor-derived exosomes (TEX) have immunoregulatory properties. Adenosine triphosphate (ATP) and its immunosuppressive precursor adenosine (ADO) have been found in cancerous tissue. We investigated the effect of TEX on B cells in the presence of ATP. TEX were isolated from human HNSCC cell line (PCI-13) cultures and co-cultured with peripheral blood B cells of healthy donors, with or without TEX in different concentrations and with or without a low (20 mu M) or high (2000 mu M) ATP dose. We were able to demonstrate that TEX inhibit B-cell proliferation. The addition of TEX to either ATP concentration showed a decreasing trend in CD39 expression on B cells in a dose-dependent manner. High ATP levels (2000 mu M) increased apoptosis and necrosis, and analysis of apoptosis-associated proteins revealed dose-dependent effects of ATP, which were modified by TEX. Altogether, TEX exhibited dual immunomodulatory effects on B cells. TEX were immunosuppressive by inhibiting B-cell proliferation; they were immunostimulatory by downregulating CD39 expression. Furthermore, TEX were able to modulate the expression of pro- and anti-apoptotic proteins. In conclusion, our data indicate that TEX play an important, but complex, role in the tumor microenvironment.
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