Fig. 2. Metabolic characteristics of MDSCs.

a | Changes in lipid and glucose metabolism that occur in myeloid-derived suppressor cells (MDSCs) and in tumour cells in the tumour environment are shown. MDSCs in the tumour microenvironment show an upregulation of fatty acid oxidation (FAO) and glycolysis and a decrease in oxidative phosphorylation (OXPHOS). They also show increased lipid accumulation and increased production of the metabolites methylglyoxal, arginine, tryptophan and cysteine. Key changes in the tumour microenvironment are depicted in the yellow boxes. b | Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in MDSCs. The UPR is characterized by an orchestrated upregulation of activating transcription factor 6 (ATF6), inositol requiring enzyme 1 (IRE1α) and PKR-like endoplasmic reticulum kinase (PERK). The transcription factor C/EBP-homologous protein (CHOP) is a critical mediator of the PERK pathway, whereas spliced X-box binding protein 1 (sXBP1) is a mediator of the IRE1α pathway. ER stress induced the expression of TNF-related apoptosis-induced ligand receptors (DR5) and lectin-type oxidized LDL receptor 1 (LOX1) and the conversion of neutrophils to polymorphonuclear MDSCs. The reduced NRF2 signalling favoured the accumulation of cytosolic mitochondrial DNA and consequent expression of antitumour type I interferon, in a STING-dependent manner⁹⁷.