Weill Cornell Medicine researchers have discovered a mechanism that ovarian tumors use to cripple immune cells and impede their attack – blocking the energy supply T cells depend on. The work, published Oct. 23 in Nature , points toward a promising new immunotherapy approach for ovarian cancer, which is notoriously aggressive and hard to treat.
A significant obstacle in treating ovarian cancer is the tumor microenvironment – the complex ecosystem of cells, molecules and blood vessels that shields cancer cells from the immune system. Within this hostile environment, T cells lose their ability to take up lipid (fat) molecules, which are necessary for energy to mount an effective attack. “T cells rely on lipids as fuel, burning them in their mitochondria to power their fight against pathogens and tumors,” said senior author, Juan Cubillos-Ruiz , the William J.
Ledger, M.D., Distinguished Associate Professor of Infection and Immunology in Obstetrics and Gynecology at Weill Cornell Medicine.
“However, the molecular mechanisms that govern this critical energy supply are still not well understood.” Lipids are abundant in ovarian tumors, but T cells seem unable to utilize them in this environment. “Researchers have focused on a protein called fatty acid-binding protein 5, or FABP5, which facilitates lipid uptake, but its exact location within the T cell remained unclear,” said first author Sung-Min Hwang, a postdoctoral associate in Cubillos-Ruiz’s lab, who led the .