The effect of immunomodulator thymosin α1 on the expression of TNBC PD-L1 through Wnt/β- catenin signaling pathway

Abstract Purpose: Explore whether thymosin affects the expression of PD-L1 on the surface of tumor cells, which in turn affects the immunotherapy of triple-negative breast cancer.Method: After treating human breast cancer MDA-MB-231 cells with different concentrations of thymosin α1, the PD-L1 expression of the cells was tested for protein and gene. Through bioinformatics analysis, the target gene was screened out, and the signal pathway that thymosin α1 might participate in was further verified.Result: After adding 130μM and 160μM of thymosin α1, the expression of PD-L1 in MDA-MB-231 cells was inhibited at 12h, 24h, 48h and 96h. The related pathways of genes down-regulated by Tα1 in KEGG are: cancer pathway, basal cell epithelioma, apoptosis, Hippo and Wnt signaling pathway; immune pathway, such as rheumatoid arthritis, bacterial infection. After MSAB treatment of the experimental group, the expression of AXIN2 was up-regulated, and the expression of β-catenin in the cells was up-regulated. Compared with the cells in the untreated experimental group, PD-L1 was up-regulated. However, we found that β-catenin in the nucleus was not significantly up-regulated, but the expression of C-myc was up-regulated.Conclusion: Thymosin α1 down-regulates the PD-L1 expression of TNBC through the Wnt/β-catenin pathway, which may affect PD-L1-dependent TNBC immunotherapy.