Thymosin alpha-1 blocks the accumulation of myeloid suppressor cells in NSCLC by inhibiting VEGF production - 28/10/20
, Wang Ma a, ⁎ Bienvenue sur EM-consulte, la référence des professionnels de santé.
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Graphical abstract |
Highlights |
• | Thymosin alpha-1 promotes the apoptosis and inhibits the migration of M-MDSCs. |
• | Thymosin alpha-1 inhibits NSCLC tumor growth. |
• | Inhibition of MDSCs chemotaxis depends on a reduction in VEGF production. |
Abstract |
Background |
Thymosin alpha-1 (TA) has been reported to inhibit tumor growth as an immunomodulator. However, its mechanism of action in immunosuppressive cells is unclear. The purpose of this study was to investigate whether TA can reshape the immune microenvironment by inhibiting the function of myeloid-derived suppressor cells (MDSCs) in non-small cell lung carcinoma (NSCLC).
Methods |
The effects of TA on peripheral blood monocytic MDSCs (M-MDSCs) in patients with NSCLC and on the apoptosis and migration of M-MDSCs were studied. A mouse subcutaneous xenograft tumor model was constructed, and the effect of TA on M-MDSC migration was evaluated. Quantitative real-time PCR, Western blotting, flow cytometry and immunohistochemistry were used to examine the mechanism by which TA affects M-MDSCs.
Results |
TA not only promoted the apoptosis of M-MDSCs by reducing the Bcl-2/BAX ratio but also and more importantly inhibited the migration of MDSCs to the tumor microenvironment by suppressing the production of vascular endothelial growth factor (VEGF) through the downregulation of hypoxia-inducible factor (HIF)-1α in tumor cells.
Conclusions |
TA may have a novel antitumor effect mediated by decreasing M-MDSC accumulation in the tumor microenvironment through reduced VEGF production.
Le texte complet de cet article est disponible en PDF.Abbreviations : TA, NSCLC, VEGF, TIME, MDSCs, M-MDSCs, PMN-MDSCs, DCs, NK, PBMCs, CFSE, 7AAD, HIF-1α, ARG1
Keywords : Thymosin alpha-1, Myeloid-derived suppressor cells, Tumor microenvironment, Non-small cell lung carcinoma, VEGF
Plan
Vol 131
Article 110740- novembre 2020 Retour au numéro
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