Mechanism of All-Trans Retinoic Acid Effect on Tumor-Associated Myeloid-Derived Suppressor Cells

摘要: Myeloid-derived suppressor cells (MDSC) play an important role in tumor escape by suppressing T-cell responses. MDSC represent a group of myeloid lineage at different stages differentiation. Increased arginase activity and production reactive oxygen species (ROS) are among the main functional characteristics these cells. Recent studies have shown that all-trans retinoic acid (ATRA) had potent eliminating cancer patients tumor-bearing mice. ATRA differentiates into mature However, mechanism this effect is unclear. Here, we dramatically specifically up-regulated gene expression protein level glutathione synthase (GSS) MDSC. This resulted accumulation (GSH) cells, observed both mice patients. Blockade GSH synthesis cancelled on Accumulation using N-acetyl-L-cysteine mimicked Analysis potential mechanisms GSS revealed regulates its not directly binding to promoter but primarily via activation extracellular signal-regulated kinase 1/2. Thus, induced differentiation neutralization high ROS novel involves specific up-regulation could be used developing monitoring therapeutic application ATRA.