T cells in pancreatic cancer stroma: Tryptophan metabolism plays an important role in immunoregulation

Several studies have shown that the immune system is highly regulated by tryptophan metabolism, which serves as an immunomodulatory factor. The indoleamine 2,3-dioxygenase 1 (IDO1), as an intracellular enzyme that participates in metabolism of the essential amino acid tryptophan in the kynurenine pathway, is an independent prognostic marker for pancreatic cancer (PC). First, overexpression of IDO1 inhibits the maturation of dendritic cells and T-cell proliferation in the liver and spleen. Second, the high expression of kynurenine induces and activates the aryl hydrocarbon receptor, resulting in upregulated programmed cell death protein 1 expression. Third, the induction of IDO1 can lead to loss of the T helper 17 cell/regulatory T cell balance, mediated by the proximal tryptophan catabolite from IDO metabolism. In our study, we found that overexpression of IDO1 upregulated CD8+ T cells and reduced natural killer T cells in pancreatic carcinoma in mice. Hence, it may be essential to pay more attention to tryptophan metabolism in patients, especially those who are tolerant to immunotherapy for PC.