Targeting Inhibition of Accumulation and Function of Myeloid-Derived Suppressor Cells by Artemisinin via PI3K/AKT, mTOR, and MAPK Pathways Enhances Anti-PD-L1 Immunotherapy in Melanoma and Liver Tumors

Figure 2

ART promotes to polarize MDSCs from M2-like protumoral phenotype towards M1-like antitumoral one. (a–g) Purified CD11b⁺Gr-1⁺ MDSCs from the tumors of B16F10 melanoma cell-bearing C57BL/6 mice treated with DMSO for 13 days or ART (50 mg/kg) for 18 days (both groups had the similar tumor volume ~1000 mm³). (a and b) Performed RNA sequencing (RNA-seq) and gene set enrichment analysis (GSEA) and (c) the expressions of M1 and M2 signature genes were detected by qPCR in tumor MDSCs. (d) The cytokines IL-6, IL-10, TNF-α, and TGF-β were detected by ELISA. (e) The expressions of p-STAT1 (Tyr701), STAT1, iNOS, ARG1, and p47^phox protein were detected by western blot. (f and g) Detected arginase activity by biochemical assays and nitric oxide content by DAF-FM DA fluorescence using flow cytometry analysis. Data are and are from a representative experiment of three (f and g) or from two (c) independent experiments. Unpaired Student’s test for (c) and (d) and (f) and (g). , , , and . ns: not significant.

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