Bi-directional metabolic reprogramming between cancer cells and T cells reshapes the anti-tumor immune response
Fig 2
Metabolic characteristics during T cell differentiation.
Upon activation, naïve T cells undergo metabolic reprogramming and differentiate into effector T cells, shifting toward aerobic glycolysis to support rapid proliferation and effector functions. This transition is accompanied by epigenetic modifications at key gene loci. Following antigen clearance, a subset of T cells differentiates into memory T cells, which revert to utilizing fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) to support long-term survival and functional readiness. By contrast, during chronic antigen stimulation, effector T cells are driven toward an exhausted state, characterized by metabolic reprogramming, mitochondrial dysfunction and impaired effector function. Regulatory T cells (Tregs), an immunosuppressive population that supports tumor progression, rely on OXPHOS and FAO for survival and exert their function through the secretion of inhibitory cytokines such as TGF-β and IL-10. ATP, adenosine triphosphate; BCAA, branched-chain amino acid; CTLA4, cytotoxic T-lymphocyte associated protein 4; FOXO1, forkhead box O1; FOXP3, forkhead box P3; GLUT-1, glucose transporter 1; HIF-1α, hypoxia-inducing factor 1α; mTOR, mammalian target of rapamycin; PD-1, programmed cell death protein 1; PGC-1α, peroxisome proliferator-activated receptor-γ coactivator 1-α; ROS, reactive oxygen species; TCA, tricarboxylic acid cycle; TCR, T cell receptor. Figure created with BioRender, https://www.biorender.com.