For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
10
views
66
references
 Top references
cited by
59
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      257
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Role of IDO and TDO in Cancers and Related Diseases and the Therapeutic Implications

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Kynurenine (Kyn) pathway is a significant metabolic pathway of tryptophan (Trp). The metabolites of the Kyn pathway are closely correlated with numerous diseases. Two main enzymes, indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO or TDO2), regulate the first and rate-limiting step of the Kyn pathway. These enzymes are directly or indirectly involved in various diseases, including inflammatory diseases, cancer, diabetes, and mental disorders. Presently, an increasing number of potential mechanisms have been revealed. In the present review, we depict the structure of IDO and TDO and explicate their functions in various diseases to facilitate a better understanding of them and to indicate new therapeutic plans to target them. Moreover, we summarize the inhibitors of IDO/TDO that are currently under development and their efficacy in the treatment of cancer and other diseases.

          Related collections

          Most cited references66

          • Record: found
          • Abstract: found
          • Article: not found

          Indoleamine 2,3 dioxygenase and metabolic control of immune responses.

          David Munn, Andrew L Mellor (2013)
          Sustained access to nutrients is a fundamental biological need, especially for proliferating cells, and controlling nutrient supply is an ancient strategy to regulate cellular responses to stimuli. By catabolizing the essential amino acid TRP, cells expressing the enzyme indoleamine 2,3 dioxygenase (IDO) can mediate potent local effects on innate and adaptive immune responses to inflammatory insults. Here, we discuss recent progress in elucidating how IDO activity promotes local metabolic changes that impact cellular and systemic responses to inflammatory and immunological signals. These recent developments identify potential new targets for therapy in a range of clinical settings, including cancer, chronic infections, autoimmune and allergic syndromes, and transplantation. Copyright © 2012 Elsevier Ltd. All rights reserved.
          Article 0 comments Cited 409 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity.

            Xiangdong Liu, Niu Shin, Holly K Koblish … (2010)
            Indoleamine 2,3-dioxygenase-1 (IDO1; IDO) mediates oxidative cleavage of tryptophan, an amino acid essential for cell proliferation and survival. IDO1 inhibition is proposed to have therapeutic potential in immunodeficiency-associated abnormalities, including cancer. Here, we describe INCB024360, a novel IDO1 inhibitor, and investigate its roles in regulating various immune cells and therapeutic potential as an anticancer agent. In cellular assays, INCB024360 selectively inhibits human IDO1 with IC(50) values of approximately 10nM, demonstrating little activity against other related enzymes such as IDO2 or tryptophan 2,3-dioxygenase (TDO). In coculture systems of human allogeneic lymphocytes with dendritic cells (DCs) or tumor cells, INCB024360 inhibition of IDO1 promotes T and natural killer (NK)-cell growth, increases IFN-gamma production, and reduces conversion to regulatory T (T(reg))-like cells. IDO1 induction triggers DC apoptosis, whereas INCB024360 reverses this and increases the number of CD86(high) DCs, potentially representing a novel mechanism by which IDO1 inhibition activates T cells. Furthermore, IDO1 regulation differs in DCs versus tumor cells. Consistent with its effects in vitro, administration of INCB024360 to tumor-bearing mice significantly inhibits tumor growth in a lymphocyte-dependent manner. Analysis of plasma kynurenine/tryptophan levels in patients with cancer affirms that the IDO pathway is activated in multiple tumor types. Collectively, the data suggest that selective inhibition of IDO1 may represent an attractive cancer therapeutic strategy via up-regulation of cellular immunity.
            Article 0 comments Cited 195 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Targeting the IDO1/TDO2–KYN–AhR Pathway for Cancer Immunotherapy – Challenges and Opportunities

              Jae Eun Cheong, Lijun Sun (2018)
              Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2) catalyze the commitment step of the kynurenine (KYN) metabolic pathway. Traditionally the immunosuppressive effect of IDO1 has been attributed mainly to reduced levels of tryptophan, which activates the kinase general control nonderepressible 2 (GCN2). Emerging data have shed light on an unexpected role of the ligand-activated transcription factor aryl hydrocarbon receptor (AhR) in transducing the tumor immune escape function imparted by IDO1 and TDO2. AhR activation by the IDO1/TDO2 product KYN leads to the generation of immune-tolerant dendritic cells (DCs) and regulatory T cells, which collectively foster a tumor immunological microenvironment that is defective in recognizing and eradicating cancer cells. Multiple IDO1 inhibitors have been evaluated in clinical trials. There are novel modalities downstream of IDO1/TDO2 for pharmacological interventions. We review recent progress and future perspectives in targeting the IDO1/TDO2-KYN-AhR signaling pathway for the development of novel cancer immunotherapies.
              Article 0 comments Cited 157 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): J Cancer
                Journal ID (iso-abbrev): J Cancer
                Journal ID (publisher-id): jca
                Title: Journal of Cancer
                Publisher: Ivyspring International Publisher (Sydney )
                ISSN (Electronic): 1837-9664
                Publication date Collection: 2019
                Publication date (Electronic): 2 June 2019
                Volume: 10
                Issue: 12
                Pages: 2771-2782
                Affiliations
                Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
                Author notes
                ✉ Corresponding author: Tao Wu, PhD, Assistant Professor, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Email: tw827@ 123456shutcm.edu.cn ; Telephone: +86-21-51322748; Fax: +86-21-51322748

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                Publisher ID: jcav10p2771
                DOI: 10.7150/jca.31727
                PMC ID: 6584917
                PubMed ID: 31258785
                SO-VID: 8a190c0e-0ff7-4856-bcc8-8c9f0c600538
                Copyright © © Ivyspring International Publisher
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                Date received : 22 November 2018
                Date accepted : 10 April 2019
                Categories
                Subject: Review

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: tryptophan,kynurenine,ido,tdo
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: tryptophan, kynurenine, ido, tdo

                Comments

                Comment on this article

                scite_

                Similar content257

                See all similar

                Cited by65

                See all cited by

                Most referenced authors1,173

                See all reference authors