The potential of targeting indoleamine 2,3-dioxygenase for cancer treatment
Johanna M Gostner1, Kathrin Becker, Florian Überall
1Medical University of Innsbruck, Biocenter, Division of Medical Biochemistry , Innsbruck 6020 , Austria.
Introduction:
Degradation of the essential amino acid tryptophan via indoleamine 2,3-dioxygenase (IDO1) represents an important antiproliferative strategy of the cellular immune response. Tryptophan shortage and accumulation of kynurenine downstream products also affect T-cell responses, providing a negative feedback control of immune activation. IDO1 activity can promote a regulatory phenotype in both T cells and dendritic cells. These phenomena can support tumor immune escape.
Areas Covered:
IDO1 activity reflects the course of several malignancies, and determination of kynurenine to tryptophan ratio in serum/plasma can be used to assess immune activation. Moreover, the accelerated breakdown of tryptophan has been correlated with the development of cancer-associated disturbances such as anemia, weight loss and depression. Tumoral IDO1 expression was correlated with a poor prognosis in several types of tumors, which makes it to an interesting target for immunotherapy. In addition, according to recent data, a role of trytptophan 2,3-dioxygenase (TDO) in tumorigenesis cannot be excluded.
Expert Opinion:
Tryptophan metabolism is critical for cell proliferation, inflammation and immunoregulation. Accelerated tryptophan breakdown favors tumor immune escape. Accordingly, targeting IDO1 by immunotherapy may represent a favorable approach; however, blocking crucial immunoregulatory pathways could also introduce the risk of immune system overactivation, finally leading to unresponsiveness.
Insights
Indoleamine 2,3-dioxygenase (IDO1) degrades tryptophan, aiding tumor immune escape. Targeting IDO1 may offer immunotherapy benefits but risks immune overactivation and unresponsiveness.
Area of Science:
- Immunology
- Biochemistry
- Oncology
Background:
- Indoleamine 2,3-dioxygenase (IDO1) degrades tryptophan, a key immune evasion strategy in tumors.
- IDO1 activity influences T-cell and dendritic cell function, promoting immune suppression.
- Accelerated tryptophan breakdown is linked to cancer progression and associated symptoms.
Purpose of the Study:
- To explore the role of tryptophan metabolism in cancer immune evasion.
- To evaluate indoleamine 2,3-dioxygenase (IDO1) as a potential immunotherapy target.
Main Methods:
- Assessing IDO1 activity through kynurenine to tryptophan ratio in serum/plasma.
- Correlating tumoral IDO1 expression with patient prognosis.
- Reviewing recent data on tryptophan 2,3-dioxygenase (TDO) in tumorigenesis.
Main Results:
- IDO1 activity is indicative of malignancy progression.
- High tumoral IDO1 expression correlates with poor prognosis.
- Tryptophan metabolism critically impacts immune regulation and tumor escape.
Conclusions:
- Targeting IDO1 offers a potential immunotherapy strategy against cancer.
- Blocking IDO1 may carry risks of immune system overactivation and unresponsiveness.
- Further research into tryptophan metabolism and IDO1/TDO pathways is warranted.
More Related Videos
10:47Harnessing the Bioorthogonal Inverse Electron Demand Diels-Alder Cycloaddition for Pretargeted PET Imaging
Published on: February 3, 2015
06:07Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:57Targeted Cancer Therapies
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:49Cancer Therapies
02:34Inhibition of Cdk Activity
01:27Tumor Immunotherapy