A Ludwig Cancer Research study has identified a metabolic switch in the immune system's T cells that is essential to the generation of memory T cells-;which confer lasting immunity to previously encountered pathogens-;and a T cell subtype found in tumors that drives anti-tumor responses during immunotherapy . Led by Ludwig Lausanne's Ping-Chih Ho and Alessio Bevilacqua and published in the current issue of Science Immunology , the study identifies PPARβ/δ, a master regulator of gene expression, as that essential molecular switch. Ho, Bevilacqua and their colleagues also show that the switch's dysfunction compromises T cell "memory" of previously encountered viruses as well as the induction of anticancer immune responses in mice.
"Our findings suggest that we might be able to engage this switch pharmacologically to improve the efficacy of cancer immunotherapies," said Ho. When killer (or CD8+) T cells, which kill sick and cancerous cells, are activated by their target antigen, they switch on metabolic pathways that most other healthy cells only use when starved of oxygen. This type of metabolism-;involving a metabolic process known as aerobic glycolysis-;supports multiple processes essential to the killer T cell's ability to proliferate and destroy its target cells.
Most killer T cells die off after they've cleared an infection. A few, however, transform into central memory CD8+ T cells (Tcms) that linger in the circulation to establish what we call immunity: the ability to .