Editorial: Targeting glucose metabolism in cancer immunity and immunotherapy.
(2023) Frontiers in Immunology — Vol. 14, n° (), p. 1171274 (2023)
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- Abstract
- Glucose catabolism through glycolysis, the TCA cycle and OXPHOS is a source of ATP and biosynthetic intermediates. In healthy cells, glucose metabolism is tightly regulated by insulin and growth factors to ensure that only the required amounts are taken up. By contrast, cancer cells often have oncogenic alterations in signaling pathways, such as PI3K/Akt activation, that enhance their ability to take up glucose from the extracellular environment. This phenomenon is known as the Warburg effect, whereby cancer cells ferment glucose into lactate, even in the presence of oxygen to support de novo generation of nucleotides, lipids, proteins and antioxidant defenses. It is important to note that glucose is not only essential for cancer cell metabolism, but also for immune cells in the tumor microenvironment. In fact, glucose competition between cancer and immune cells can have a profound impact on the ability of the latter to generate an efficient immune response against the tumor. For example, upon activation, T cells undergo metabolic reprogramming characterized by a shift from oxidative catabolic metabolism in naive T cells to anabolic glycolytic metabolism. This shift in metabolic preferences helps to meet the energy and biosynthetic demands required for T cell proliferation and effector functions. Glucose competition within the tumor microenvironment can therefore reduce the capacity of T cells to produce important cytokines such as IFN-γ, thereby diminishing their ability to mount an efficient immune response. Thus, understanding the complex interplay between glucose metabolism and the immune response in the tumor microenvironment is crucial for developing effective cancer immunotherapies.
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Citations
Feron, O., Chang, C.-H., & Végran, F. (2023). Editorial: Targeting glucose metabolism in cancer immunity and immunotherapy. Frontiers in Immunology, 14(()), 1171274. https://doi.org/10.3389/fimmu.2023.1171274 (Original work published 2023)