Our body is made up of millions of cells that coordinate daily function. They are constantly working to maintain activity and keep us healthy. Cells activate, proliferate, and conduct specialized responsibilities dependent on their differentiated state. As a result, they need energy to carry out these functions. Cells get their energy through a process known as metabolism. It breaks down macromolecules to fuel activity. Glucose or sugar is a primary source for power and energy, particularly in immune cells. During an increased uptake of sugar, there is a metabolic shift, and these cells can generate energy through a process known as ‘glycolysis’. Similarly, when cancer is present, tumor cells become dependent on glycolysis although there are limited nutrients in the area. This phenomenon is known as the “Warburg Effect”, named after the scientist who observed this occurrence. Additionally, inappropriate amounts of glucose can have deleterious effects on cells and the body overall. Metabolism can occur in different ways and scientists are still working to understand how different cells obtain energy in various contexts, including cancer.
A recent paper in Cell Metabolism, by Dr. Russell Jones and others, demonstrated that glucose can improve anti-cancer immune cells and boost their communication throughout the body. Jones is the Professor and Chair of the Department of Metabolism and Nutritional Programming at the Van Andel Institute. He is a world-renowned expert on cancer metabolism and immunology. His work focuses on how cancer and immune cells fuel themselves through different cellular pathway interactions. Jones’ goal is to exploit these mechanisms to improve therapy and patient care.
The immune cells the researchers observed are known as ‘CD8+ T cells’. Specifically, these immune cells are directly responsible for identifying and targeting pathogens. However, in the context of cancer, different molecules and proteins prevent these cells from functioning with the assistance of immune suppressive cells.
Researchers discovered why glucose is necessary for CD8+ T cell function. Previously it was thought that T cells break down glucose for energy. However, Jones and his team discovered that CD8+ T cells use glucose to help build other molecules that are necessary to support an anti-tumor response. Specifically, glucose is used to build large sugar-fat compounds known as ‘glycosphingolipids’. This compound helps T cells grow and generate an anti-tumor response. Glycosphingolipids form structures within the cell membrane to help amplify cell signaling, which instruct the T cell to target cancer. Without glycosphingolipids cell signaling becomes weak. Consequently, tumor response is weak as CD8+ T cells lose their anti-tumor function.
This discovery by Jones and others has major implications in the field of cancer treatment. By understanding how T cells use glucose to target cancer, researchers can improve the fitness of T cell therapy. Moreover, it provides foundational knowledge about T cell biology necessary to effectively target tumors. This work is paradigm-shifting as it changes our preconceived notion of how T cell use glucose in the context of cancer. As a result, the mechanism behind glucose consumption can improve standard of care therapy and patient survival.