Metabolic Reprogramming of Glycolysis, Lipids, and Amino Acids in Tumors: Impact on CD8+ T Cell Function and Targeted Therapeutic Strategies

Tumor cells undergo metabolic reprogramming to support their rapid proliferation and to adapt to the challenges of the tumor microenvironment (TME). This involves significant changes in glycolysis, lipid, and amino acid metabolism, which not only promote tumor survival but also impact CD8+ T cells within the TME. This review examines how these metabolic alterations affect CD8+ T cell function, particularly through competition for energy resources and microenvironmental changes. For instance, aerobic glycolysis in tumor cells depletes glucose and leads to lactate accumulation, both of which suppress CD8+ T cell activity. Additionally, changes in lipid metabolism affect the composition of cell membranes and disrupt signal transduction, impairing T cell function. Amino acid reprogramming, such as increased consumption of glutamine and arginine by tumor cells, further hinders the activity and proliferation of CD8+ T cells. We also explore therapeutic strategies that target these metabolic pathways in tumor cells, such as inhibitors of glycolysis and fatty acid synthesis, which may enhance the antitumor activity of CD8+ T cells. These approaches show promise in improving both T cell function and the effectiveness of immune checkpoint blockade therapies. By investigating the link between tumor metabolism and CD8+ T cell dysfunction, this review highlights mechanisms of tumor immune evasion. This understanding can guide the development of novel immunotherapies aimed at enhancing T cell function within the TME.