STAT3 and breast cancer: In addition, metformin downregulates ROS production of through inhibition of mitochondrial complex I (174, 175), and possesses anti-inflammatory and immunomodulatory activity, affecting energy metabolism of immune cells and stimulating CD8+ tumor infiltrating lymphocytes leading to a cytotoxic response against cancer cells (176); moreover, metformin enhances immune response in vivo in mouse melanoma model (177), and inhibits NF-κB nuclear localization and Stat3 activity in breast cancer CSCs (178).