Fig. 5

Metabolic alterations in tumor-associated dendritic cells (TADCs) during tumor progression. TADCs encounter hypoxia and tumor-derived damage-associated molecular patterns (DAMPs) to upregulate glycolysis via an initial TBK1-IKKε pathway and/or later PI3K-AKT-HIF1α pathway. HIF1α impairs the maturation of DC cells and upregulates the expression of A2b and NO (which inhibits OXPHOS). A2b-adenosine interaction induces immunosuppressive cytokines (e.g., TGF-b and IL-10) and pro-tumor cytokines (e.g., IL-6 and IL-8) that promote tumor growth. Nutrient deprivation-induced AMPK activation and lactate accumulation suppress glycolysis and upregulate OXPHOSP in TADCs. In addition, amino acid uptake, metabolism, and lipid accumulation promote immunosuppressive events that lead to tumor growth