ARG1 and neoplasm: Different pre-clinical and clinical evidence also showed that metformin administration inhibited MDSCs’ accumulation and immunosuppressive functions through several mechanisms, such as reduction in STAT3 phosphorylation, ARG1 and ROS production [233], decrease in CXCL1 secretion by tumor cells [234] and downregulation of ectonucleotidases CD39/CD73 catalyzing adenosine production, which confers immunosuppressive functions to MDSCs [235].