Bi-directional metabolic reprogramming between cancer cells and T cells reshapes the anti-tumor immune response
Fig 3
Metabolic interplay of cancer cells and T cells in the TME.
The tumor microenvironment (TME) is enriched with immunosuppressive cell populations such as regulatory T cells (Tregs), which promote tumor progression and suppress anti-tumor immunity through metabolic reprogramming and the secretion of inhibitory factors, such as TGF-β and IL-10. Tumor cells further contribute to immune dysfunction by outcompeting effector T cells for critical nutrients, including oxygen, glucose and amino acids, thereby impairing T cell infiltration, effector function and cytotoxicity. Moreover, the accumulation of tumor-derived metabolites such as lactate, which suppresses T cell proliferation and function, yet may support T cell stemness, profoundly reshapes the immune landscape. Additional metabolites, including kynurenine, fumarate and succinate, further contribute to CD8+ T cell dysfunction and exhaustion. Collectively, these factors establish a metabolically hostile and immunosuppressive milieu that impairs effective antitumor immune responses. MCT, monocarboxylate transporter; PD-1, programmed cell death protein 1; PGE2, prostaglandin E2. Figure created with BioRender, https://www.biorender.com.