Indoleamine-2,3 dioxygenase: a fate-changer of the tumor microenvironment

Indoleamine-2,3 dioxygenase is a rate-limiting enzyme in the tryptophan catabolism in kynurenine pathways that has an immunosuppressive effect and supports cancer cells to evade the immune system in different cancer types. Diverse cytokines and pathways upregulate the production of indoleamine-2,3 dioxygenase enzymes in the tumor microenvironment and cause more production and activity of this enzyme. Ultimately, this situation results in anti-tumor immune suppression which is in favor of tumor growth. Several inhibitors such as 1-methyl-tryptophan have been introduced for indoleamine-2,3 dioxygenase enzyme and some of them are widely utilized in pre-clinical and clinical trials. Importantly at the molecular level, indoleamine-2,3 dioxygenase is positioned in a series of intricate signaling and molecular networks. Here, the main objective is to provide a focused view of indoleamine-2,3 dioxygenase enhancer pathways and propose further studies to cover the gap in available information on the function of indoleamine-2,3 dioxygenase enzyme in the tumor microenvironment.

Automated summary

Indoleamine-2,3 dioxygenase is an enzyme that plays a role in the catabolism of tryptophan and has immunosuppressive effects, allowing cancer cells to evade the immune system. Various cytokines and pathways increase the production of indoleamine-2,3 dioxygenase in the tumor microenvironment, leading to anti-tumor immune suppression. Inhibitors have been developed for this enzyme and are being tested in clinical trials. Further research is needed to understand the function of indoleamine-2,3 dioxygenase in the tumor microenvironment.