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.
This proposed study aims to investigate a mechanism for ethanol-promoted mammary tumor formation by using a mammary tumorigenesis mouse model. Ethanol exposure may compromise host anti-tumor immunity, which in turn promotes an immune escape of tumor cells from the surveillance of immune system. The idea has never been investigated before and will provide valuable information for further study the mechanism underlying ethanol-promoted mammary tumorigenicity.
