Metabolic Checkpoints in CD8 + T Cells within the Tumor Microenvironment: A Comprehensive Review and Emerging Insights

In recent years, a growing number of evidence suggests that cancer is a metabolic disease.Metabolic reprogramming is a hallmark of the TME, where various nutrients, including glucose, lipids, and amino acids, play key roles in regulating tumor development by acting on both tumor cells and immune cells.T cells are the core mediators of anti-tumor immunity.Especially CD8 + T cells are considered the primary immune cells involved in the anti-tumor immune response.Upon stimulation by tumor antigens and other immune cells, CD8 + T cells undergo metabolic reprogramming through signaling pathways.Metabolites or metabolic checkpoints induce epigenetic changes in key genes, altering the differentiation and effector function of CD8 + T cells.This review first elaborates on the anti-tumor functional characteristics and metabolic profiles of CD8 + T cells at different stages of differentiation in the TME.Then we focus on the roles of key metabolites and metabolic checkpoints in shaping CD8 + T cell differentiation, functionality, and immune responses, specifically through glucose, lipid, and amino acid metabolism.Finally, we discuss the reasons for heterogeneity in the effects of metabolic checkpoints on CD8 + T cells and explore potential clinical applications of metabolic checkpoints in treatment.Understanding the correlation between CD8 + T cell metabolism and anti-tumor immunotherapy may facilitate the development of new strategies to enhance the efficacy of CD8 + T cell-based cancer treatments.