Alcohol consumption is a well-known risk factor for human cancer, including female breast cancer. The biological and epidemiological evidence indicates that alcohol consumption is causally and dose-dependently associated with breast cancer. However, the mechanism underlying ethanol-promoted mammary carcinogenesis is unclear. Cancer is a systemic disease. The immune system monitors the host body recognizing and reacting against newly arising mutated/tumor cells to stop/control tumor formation. A process termed “immunoediting” is initiates when the immune system encounters mutated/tumor cells and may result in one of the three outcomes: elimination, equilibrium or escape of tumor cells from immune control. Hence, tumor formation indicates a compromise of host immunosurveillance. T cells, particularly cytotoxic T cells, represent a major component of cell-mediated anti-tumor immunity. One of the mechanisms modulating T cell antitumor effector function involves the activation/inhibition receptors on a T cell membrane. Inhibition of T cell antitumor function through the activation of immune checkpoint pathways, such as PD-L1/PD-1 pathway, has been shown to promote tumor cell immune escape and tumorigenesis. In addition, previous reports indicate that the aberrant activation of STAT3 may up-regulate PD-L1 in many human tumors. The proposed study will test our hypothesis that ethanol promotes mammary tumorigenesis through STAT3/PD-L1/PD-1-mediated inhibition of T cell antitumor function.