Metabolic regulatory pathways of MDSCs in the TME. Under hypoxic conditions, metabolic genes are upregulated, and increased metabolism enhances the suppressive function of MDSCs. MDSCs increase the uptake of extracellular nutrients, such as glucose, FA, glutamine and acetate, which are required for glycolysis, the TCA cycle, FAO, fatty acid synthesis and amino acid synthesis. Furthermore, excessive lactate, generated by tumor cells, can also be transported into MDSCs to participate in metabolism. FA, fatty acid; TCA cycle, tricarboxylic acid cycle; FAO, fatty acid oxidation; FFAs, free fatty acids; MCT1, monocarboxylate transporter 1; GLUT1, glucose transporter 1; G-6-P, glucose-6-phosphate; F-6-P, fructose-6-phosphate; F-1,6-P, fructose-1,6-bisphosphate; G-3-P, glyceraldehyde-3-phosphate; LDH, lactate dehydrogenase; PDH, pyruvate dehydrogenase; DHAP, dihydroxyacetone phosphate; CPT1, carnitine palmitoyltransferase 1; α-KG, alpha-ketoglutarate; mTOR, mammalian target of rapamycin; HIF-1α, hypoxia-inducible factor 1-alpha; AMPK, AMP-activated protein kinase; PPARγ, peroxisome proliferator-activator receptors gamma; GSH, glutathione; ASCT2, alanine-serine-cysteine transporter 2.