Glucose helps T cells build cancer-fighting structures, not just provide energy

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 is published 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.”