Thymosin alpha-1 blocks the accumulation of myeloid suppressor cells in NSCLC by inhibiting VEGF production.
Yang. Zhenzhen Z; Guo. Jiacheng J; Cui. Kang K; Du. Yabing Y; Zhao. Huan H; Zhu. Lili L; Weng. Lanling L; Tang. Wenxue W; Guo. Jiancheng J; Zhang. Tengfei T; Shi. Xiaojing X; Zong. Hong H; Jin. Shuiling S; Ma. Wang W
Key Findings
- TA promotes apoptosis of monocytic MDSCs by decreasing the Bcl‑2/BAX ratio.
- TA suppresses VEGF production in tumor cells by down‑regulating HIF‑1α, which reduces MDSC migration to the tumor.
- Overall, TA reduces the accumulation of immunosuppressive M‑MDSCs in the tumor microenvironment, suggesting a novel anti‑tumor mechanism.
Practical Outcomes
- For self‑directed health optimizers, TA shows potential as an immune‑modulating agent that could help fight cancer by targeting suppressive immune cells, but the study provides no dosing or safety guidance for personal use. It remains a pre‑clinical finding, so any experimentation should be approached with caution and ideally under medical supervision.
Summary
Thymosin alpha‑1 (TA) can make certain immune cells that help tumors (called monocytic MDSCs) die more easily and stop them from moving into the tumor by lowering a growth factor (VEGF) that tumors use. This effect happens because TA reduces a protein (HIF‑1α) that normally boosts VEGF. The result is fewer tumor‑supporting cells in the cancer environment.
Abstract
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). 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. 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. TA may have a novel antitumor effect mediated by decreasing M-MDSC accumulation in the tumor microenvironment through reduced VEGF production.
Study Information
pubmed
2020
2020-09-14T00:00:00.000Z
10.1016/j.biopha.2020.110740
10
41