Study in mice finds decreased glucose metabolism increases immune potential
Regulating glucose metabolism in immune cells may extend and enhance their ability to fight cancer and infection, according to a new mouse model study by NCI investigators. Prior to this work, the relationship between glucose metabolism and memory T cells, which play a major role in cellular immunity, was unclear. Investigating the mechanism of glucose metabolism in CD8+ T cells, whose role is to destroy virally infected cells or tumor cells, the scientists found that varying levels of glucose acted as a metabolic regulator in whether or not the cells became more specialized.
The scientists’ conclusion was supported by three main lines of evidence. First, activated CD8+ T cells experienced a divergent fate when transplanted into live mice and sorted based on differences in glucose metabolism. CD8+ T cells that displayed high glucose activity tended to be short-lived, while those with a low glucose metabolism established immunological memory and hence the ability to rapidly mount an immune defense if reinfection occurs. Second, forcing higher glucose metabolic levels severely impaired the ability of CD8+ T cells to persist and form memory in the mice. Third, and most important, specific drug inhibition of glucose metabolism with 2-deoxyglucose enhanced the ability of CD8+ T cells to become long-lived memory cells. These findings may have important implications for T cell-based therapies and vaccines for cancer and infectious diseases, since they indicate that drug targeting of metabolic pathways during the initial stages of T cell activation may enhance CD8+ T cell immunity, and hence greater overall cellular health. The work, by Madhusudhanan Sukumar, Ph.D., Nicholas P. Restifo, M.D., and Luca Gattinoni, M.D., Center for Cancer Research, NCI, appeared online Sept. 16, 2013, in the Journal of Clinical Investigation.