STAT3 Activation-Induced Fatty Acid Oxidation in CD8+ T Effector Cells Is Critical for Obesity-Promoted Breast Tumor Growth
Researchers at the City of Hope Comprehensive Cancer Center and their collaborators have investigated the impact of obesity on immune function, finding that the metabolism of immune cells is altered and affects their capacity to suppress breast cancer. They report that increased metabolism of fatty acids by a set of immune cells, CD8+ T effector cells, compromises their antitumor function. The increased fatty acid oxidation is driven in part by the hormone, leptin, which is produced by fat tissue and activates a transcription factor known as STAT3 in T effector cells. In addition, the immune checkpoint protein, PD-1, also promotes fatty acid oxidation through STAT3, further inhibiting T cell antitumor immunity. Their work provides a mechanistic link between obesity and breast cancer through leptin and increased oxidation of fatty acids in T effector cells. These findings may lead to novel therapeutics to reactivate T cells to facilitate their control of obesity-associated breast cancer progression.