fig4

Figure 4. Metabolic reprogramming in HCC shapes an immunosuppressive microenvironment by modulating Tregs and MDSCs. Under nutrient deprivation, HCC cells activate ketolysis to maintain energy supply, suppressing AMPK activity and inhibiting Tregs for rapid energy acquisition, HCC cells produce lactate via the Warburg effect; this lactate promotes Treg differentiation by activating HIF-1α. α-KG from glutamine metabolism enhances Treg function. HCC-derived factors (e.g., GM-CSF, IL-6) expand bone marrow myeloid precursors, increasing MDSCs. MDSCs infiltrating the TME suppress antitumor immunity through IDO, TGF-β, and IL-10, thereby modulating Treg activity. HCC: Hepatocellular carcinoma; Tregs: regulatory T cells; MDSCs: myeloid-derived suppressor cells; AMPK: AMP-activated protein kinase; HIF-1α: hypoxia-inducible factor 1α; α-KG: α-ketoglutarate; GM-CSF: granulocyte–macrophage colony-stimulating factor; IL-6: interleukin-6; TME: tumor microenvironment; IDO: indoleamine 2,3-dioxygenase; TGF-β: transforming growth factor β; IL-10: interleukin-10; ROS: reactive oxygen species; RNS: reactive nitrogen species.