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Indoleamine-2,3 dioxygenase: a fate-changer of the tumor microenvironment
Parviz Azimnasab-Sorkhabi1, Maryam Soltani-Asl2, Túlio Teruo Yoshinaga2
1Department of Surgery, School of Veterinary Medicine and Animal Sciences, University of Sao Paulo, Sao Paulo, Brazil. Sorkhabi.parviz@gmail.com.
Abstract:
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.
Insights
Indoleamine-2,3 dioxygenase (IDO) is an enzyme that helps cancer evade immune attack. This review focuses on IDO-enhancing pathways in the tumor microenvironment to identify new therapeutic strategies.
Area of Science:
- Biochemistry
- Immunology
- Oncology
Background:
- Indoleamine-2,3 dioxygenase (IDO) is a key enzyme in tryptophan catabolism via kynurenine pathways.
- IDO exhibits immunosuppressive properties, aiding cancer cells in immune evasion across various cancer types.
- Elevated IDO production and activity in the tumor microenvironment contribute to anti-tumor immune suppression and promote tumor growth.
Purpose of the Study:
- To provide a focused overview of pathways that enhance indoleamine-2,3 dioxygenase (IDO) activity.
- To highlight the role of IDO in the tumor microenvironment.
- To identify gaps in knowledge and suggest future research directions for IDO function in cancer.
Main Methods:
- Literature review focusing on IDO-enhancing pathways.
- Analysis of molecular and signaling networks involving IDO.
- Synthesis of current understanding of IDO in cancer immunology.
Main Results:
- IDO is upregulated by diverse cytokines and pathways within the tumor microenvironment.
- IDO activity leads to significant anti-tumor immune suppression.
- IDO inhibitors, like 1-methyl-tryptophan, are under investigation in pre-clinical and clinical trials.
Conclusions:
- Understanding IDO-enhancer pathways is crucial for developing effective cancer immunotherapies.
- Further research is needed to fully elucidate the intricate role of IDO in the tumor microenvironment.
- Targeting IDO represents a promising strategy to overcome immune evasion in cancer.
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