Fig. 3

Metabolic alterations regulate immunosuppression in metastatic PDAC. The metabolic microenvironment in pancreatic tumors changes with disease progression. A, B Altered Trp catabolism due to upregulated IDO1 result in high kynurenine levels which activates AhR to promote enrichment of Tregs and M2-TAMs, resulting in  enhanced immunosuppression in the TME. C, D Metabolic byproducts and high levels of non-essential AA (serine/arginine) and extracellular methionine enhance immunosuppression in PDAC tumors. E, F Increased immunosuppression is associated with immune dysfunction, immune evasion, and metastasis. Abbreviations: Trp- tryptophan; AhR-aryl hydrocarbon receptor; IDO1- indoleamine 2, 3-dioxygenase 1; ExNEAA- extracellular non-essential amino acid; PD1- programmed cell death receptor 1; CTLA4- cytotoxic T-lymphocyte antigen-4; iNOS- inducible nitric oxide synthase; Met- methionine; Ser- serine; Arg- arginine; SAM- S-adenosyl methionine