Kyoto, Japan -- Cancer immunotherapy is a type of cancer treatment that harnesses the immune system to fight cancer cells. The treatment involves CD8⁺ T cells, also known as killer T cells, which play a crucial role in attacking tumors. Unfortunately, these cells gradually become exhausted within the tumor microenvironment and lose their full functionality.
The exhaustion of killer T cells is linked to an imbalance in energy metabolism involving glycolysis, the breakdown of glucose into energy, and fatty acid oxidation, or FAO, the breakdown of fatty acids. Previous studies have established that glycolysis drives killer T cells toward terminal exhaustion while FAO can hinder this progression. Yet scientists still don't entirely understand how these two processes are balanced, how this contributes to terminal exhaustion, and how FAO contributes to anti-tumor immunity.
This motivated a team of researchers from Kyoto University to investigate this conundrum. A key physiological role of FAO is the consumption of fatty acids, so the team hypothesized that impaired FAO leads to intracellular fatty acid accumulation, thereby promoting toxic lipid peroxidation. The team focused on active aldehydes, the end products of lipid peroxidation, whose roles in immune cells have not been fully understood.
