image: Glucose is more than just an essential fuel for T cells — significant amounts of glucose also are used to build large molecules called glycosphingolipids (GSLs). These sugar-fat compounds are essential for T cell growth, internal communication and making proteins that T cells use to combat cancer. The findings, published in Cell Metabolism by Van Andel Institute scientists, offer a potential path toward improving T cells’ ability to fight cancer and infection. Image credit: Gabrielle Eisma.
Credit: Courtesy of Van Andel Institute. Image by Gabrielle Eisma.
GRAND RAPIDS, Mich. (Aug. 5, 2025) — For cancer- and infection-fighting T cells, glucose offers far more than a simple sugar rush.
A new discovery by Van Andel Institute scientists reveals that glucose, an essential cellular fuel that powers immune cells, also aids in T cells’ internal communication and boosts their cancer-fighting properties. The findings may help optimize T cells’ ability to combat cancer and other diseases.
A study describing the work published today in Cell Metabolism.
“Immune cells are highly influenced by their environment” said Joseph Longo, Ph.D., the study’s first author and a postdoctoral fellow in the lab of Russell Jones, Ph.D. “We knew that T cells need access to glucose to function, but we didn’t know exactly why. It was previously thought that T cells mainly break down glucose for energy, but our new work shows that T cells use glucose as a building block for other molecules that are necessary to support T cells’ anti-cancer properties.”
The findings reveal that T cells allocate significant portions of glucose to build large molecules called glycosphingolipids (GSLs). These sugar-fat compounds are essential for T cell growth and making proteins that T cells use to combat cancer.
GSLs help form fat-rich structures on T cell surfaces called lipid rafts, which bring together cell signaling proteins that instruct the T cell to kill cancer cells. Without GSLs, these signals are weaker, making T cells less effective at destroying tumors.
“Both T cells and cancer cells leverage different nutrients to support varying aspects of their function,” Jones said. “The more we know about these different fuel sources, the better we can support T cells’ innate cancer-fighting abilities while also developing ways to possibly make cancer cells more vulnerable to immune attack.”
Other authors include Lisa M. DeCamp, Brandon M. Oswald, Ph.D., Robert Teis, Alfredo Reyes-Oliveras, Ph.D., Michael S. Dahabieh, Ph.D., Abigail E. Ellis, Michael P. Vincent, Ph.D., Hannah Damico, M.B., Kristin L. Gallik, Ph.D., Nicole M. Foy, Shelby E. Compton, Ph.D., Colt D. Capan, M.S., Kelsey S. Williams, Ph.D., Corinne R. Esquibel, Ph.D., Zachary B. Madaj, M.S., Hyoungjoo Lee, Ph.D., Connie Krawczyk, Ph.D., Brian B. Haab, Ph.D., and Ryan D. Sheldon, Ph.D., of VAI; and Dominic G. Roy, Ph.D., of Université de Montréal.
Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award no. R01AI165722 (Jones). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Journal
Cell Metabolism
Article Title
Glucose-dependent glycosphingolipid biosynthesis fuels CD8+ T cell function and tumor control
Article Publication Date
5-Aug-2025