Regulation of ROS in myeloid-derived suppressor cells through targeting fatty acid transport protein 2 enhanced anti-PD-L1 tumor immunotherapy

Despite the remarkable success and efficacy of immune checkpoint blockade (ICB) therapy against PD-1/PD-L1 axis, it induces sustained responses in a sizeable minority cancer patients due to activation immunosuppressive factors such as myeloid-derived suppressor cells (MDSCs). Inhibiting function MDSCs is critical for successful ICB therapy. Interestingly, lipid metabolism crucial factor modulating function. Fatty acid transport protein 2 (FATP2) conferred PMN-MDSCs via upregulation arachidonic metabolism. However, whether regulating accumulation by targeting FATP2 could block reactive oxygen species (ROS) production enhance PD-L1 blockade-mediated tumor immunotherapy remains unexplored. Here we report that regulated accumulation, ROS, tumor-bearing mice. Tumor cells-derived granulocyte macrophage-colony stimulating (GM-CSF) induced expression STAT3 signaling pathway. Pharmaceutical lipofermata decreased reduced blocked activity, consequently inhibited growth. More importantly, inhibition enhanced anti-PD-L1 CD107a on tumor-infiltrating CD8+ T-cells. Furthermore, combination MDSC's suppressive role T- thereby T-cell's ability IFN-?. These findings indicate plays key accumulation-induced ROS provides novel therapeutic approach immunotherapy.