Relationship between interferon‐γ, indoleamine 2,3‐dioxygenase, and tryptophan catabolism

  title={Relationship between interferon‐$\gamma$, indoleamine 2,3‐dioxygenase, and tryptophan catabolism},
  author={Milton W. Taylor and Gensheng Feng},
  journal={The FASEB Journal},
  pages={2516 - 2522}
Interferons have been shown to be potential anti‐cancer agents and to inhibit tumor cell growth in culture. The in vivo mechanism of the anti‐proliferative effect may be direct or indirect through the immune system; however, in vitro a primary mechanism of cytotoxicity is through the depletion of tryptophan. In particular, interferon‐γ (IFN‐γ) induces an enzyme of tryptophan catabolism, indoleamine 2,3‐dioxygenase (IDO), which is responsible for conversion of tryptophan and other indole… 

Indoleamine 2,3-Dioxygenase Activity-Induced Acceleration of Tumor Growth, and Protein Kinases-Related Novel Therapeutics Regimens.

  • A. EnginA. Engin
  • Biology, Medicine
    Advances in experimental medicine and biology
  • 2021
Indoleamine 2,3-dioxygenase immunostaining is strongly recommended for the identification of higher IDO producing tumors, and IDO inhibitors should be included in post-operative complementary therapy in IDO positive cancer cases only.

Indoleamine 2,3‐dioxygenase in T‐cell tolerance and tumoral immune escape

The work defining IDO as an important mediator of peripheral tolerance is surveyed, evidence of IDO dysregulation in cancer cells is reviewed, and an overview of the development ofIDO inhibitors as a new immunoregulatory treatment modality for clinical trials is provided.

Indoleamine 2,3-dioxygenase in cancer: targeting pathological immune tolerance with small-molecule inhibitors

Key studies that implicate IDO as an important mediator of peripheral immune tolerance as well as the development of a promising new anticancer modality that incorporates the use of IDO inhibitors are summarized.


It is assumed that the interactions between IDO, tryptophan and its catabolites largely determine a development of hyper-suppressor state in tumor growth and a hypo- (or lack of) suppressor status in autoimmune and allergic diseases.

Indoleamine 2,3‐dioxygenase in transplantation (Review Article)

Indoleamine 2,3‐dioxygenase is an interferon‐γ‐inducible intracellular enzyme which catalyses the catabolism of tryptophan, which has immunodulatory effects including suppressing lymphocyte responses particularly by sensitizing them to apoptosis.

Immune Escape: Role of Indoleamine 2,3-Dioxygenase in Tumor Tolerance

This chapter surveys work defining IDO as an important mediator of peripheral tolerance, reviews evidence of IDO dysregulation in cancer cells, and provides an overview of the development ofIDO inhibitors as a new immunoregulatory modality to enter clinical trials for cancer treatment.

Indoleamine 2,3‐dioxygenase: From catalyst to signaling function

Exposure of mouse plasmacytoid DCs to transforming growth factor β provides IDO with regulatory effects that are distinct, in nature, from its enzymic activity, and a nonenzymic function of IDO contributes to TGF‐β–driven tolerance.

Fludarabine Downregulates Indoleamine 2,3-Dioxygenase in Tumors via a Proteasome-Mediated Degradation Mechanism

Interestingly, fludarabine was efficient in suppressing protein expression and consequently IDO activity in two different cell lines derived from breast cancer and melanoma when IDO was activated with interferon-gamma or supernatants prepared from activated T lymphocytes.

Indoleamine 2,3-dioxygenase, an emerging target for anti-cancer therapy.

Results, coupled with data showing that increased IDO expression is an independent prognostic variable for reduced overall survival in cancer patients, suggest that IDO inhibition may represent an effective strategy to treat malignancies, either alone or in combination with chemotherapeutics or other immune based therapies.


The main mechanism by which IDO protects fetus is through reducing the tryptophan level and suppressing the T cell activity in the feto-maternal interface.