For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
12
views
185
references
 Top references
cited by
3
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      510
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The kynurenine pathway presents multi-faceted metabolic vulnerabilities in cancer

      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

          The kynurenine pathway (KP) and associated catabolites play key roles in promoting tumor progression and modulating the host anti-tumor immune response. To date, considerable focus has been on the role of indoleamine 2,3-dioxygenase 1 (IDO1) and its catabolite, kynurenine (Kyn). However, increasing evidence has demonstrated that downstream KP enzymes and their associated metabolite products can also elicit tumor-microenvironment immune suppression. These advancements in our understanding of the tumor promotive role of the KP have led to the conception of novel therapeutic strategies to target the KP pathway for anti-cancer effects and reversal of immune escape. This review aims to 1) highlight the known biological functions of key enzymes in the KP, and 2) provide a comprehensive overview of existing and emerging therapies aimed at targeting discrete enzymes in the KP for anti-cancer treatment.

          Related collections

          Most cited references185

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

          Cancer immunoediting: from immunosurveillance to tumor escape.

          Gavin Dunn, Allen T. Bruce, Hiroaki Ikeda … (2002)
          The concept that the immune system can recognize and destroy nascent transformed cells was originally embodied in the cancer immunosurveillance hypothesis of Burnet and Thomas. This hypothesis was abandoned shortly afterwards because of the absence of strong experimental evidence supporting the concept. New data, however, clearly show the existence of cancer immunosurveillance and also indicate that it may function as a component of a more general process of cancer immunoediting. This process is responsible for both eliminating tumors and sculpting the immunogenic phenotypes of tumors that eventually form in immunocompetent hosts. In this review, we will summarize the historical and experimental basis of cancer immunoediting and discuss its dual roles in promoting host protection against cancer and facilitating tumor escape from immune destruction.
          Article 0 comments Cited 791 times – based on 0 reviews     Review now
            Bookmark
            • 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 426 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase.

              David H Munn, Madhav D Sharma, Babak Baban … (2005)
              Indoleamine 2,3 dioxygenase (IDO) catabolizes the amino acid tryptophan. IDO-expressing immunoregulatory dendritic cells (DCs) have been implicated in settings including tumors, autoimmunity, and transplant tolerance. However, the downstream molecular mechanisms by which IDO functions to regulate T cell responses remain unknown. We now show that IDO-expressing plasmacytoid DCs activate the GCN2 kinase pathway in responding T cells. GCN2 is a stress-response kinase that is activated by elevations in uncharged tRNA. T cells with a targeted disruption of GCN2 were not susceptible to IDO-mediated suppression of proliferation in vitro. In vivo, proliferation of GCN2-knockout T cells was not inhibited by IDO-expressing DCs from tumor-draining lymph nodes. IDO induced profound anergy in responding wild-type T cells, but GCN2-knockout cells were refractory to IDO-induced anergy. We hypothesize that GCN2 acts as a molecular sensor in T cells, allowing them to detect and respond to conditions created by IDO.
              Article 0 comments Cited 421 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Ricardo A. León-Letelier: URI : https://loop.frontiersin.org/people/1025818Role: Role: Role:
                Rongzhang Dou: URI : https://loop.frontiersin.org/people/1910980Role: Role:
                Jody Vykoukal: Role:
                Ali Hussein Abdel Sater: URI : https://loop.frontiersin.org/people/2374689Role:
                Edwin Ostrin: URI : https://loop.frontiersin.org/people/653167Role:
                Samir Hanash: URI : https://loop.frontiersin.org/people/1473085Role:
                Johannes F. Fahrmann: URI : https://loop.frontiersin.org/people/868544Role: Role: Role: Role: Role:
                Journal
                Journal ID (nlm-ta): Front Oncol
                Journal ID (iso-abbrev): Front Oncol
                Journal ID (publisher-id): Front. Oncol.
                Title: Frontiers in Oncology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 2234-943X
                Publication date (Electronic): 09 October 2023
                Publication date Collection: 2023
                Volume: 13
                Electronic Location Identifier: 1256769
                Affiliations
                [1] 1 Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center , Houston, TX, United States
                [2] 2 Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX, United States
                Author notes

                Edited by: Juan Carlos Gallardo-Pérez, National Institute of Cardiology Ignacio Chavez, Mexico

                Reviewed by: Claudia Volpi, University of Perugia, Italy; Dyah Laksmi Dewi, Gadjah Mada University, Indonesia

                *Correspondence: Johannes F. Fahrmann, jffahrmann@ 123456mdanderson.org

                †These authors have contributed equally to this work

                Article
                DOI: 10.3389/fonc.2023.1256769
                PMC ID: 10591110
                PubMed ID: 37876966
                SO-VID: 0b861de9-a960-4206-83fc-475b9adb3f4a
                Copyright © Copyright © 2023 León-Letelier, Dou, Vykoukal, Sater, Ostrin, Hanash and Fahrmann
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 11 July 2023
                Date accepted : 22 September 2023
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 185, Pages: 21, Words: 8940
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Work was supported by the generous philanthropic contributions to The University of Texas MD Anderson Cancer Center Moon Shots Program™.
                Categories
                Subject: Oncology
                Subject: Review
                Custom metadata
                section-in-acceptance Cancer Metabolism

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: kynurenine pathway (kp),cancer,metabolism,therapeutics,immune evasion
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: kynurenine pathway (kp), cancer, metabolism, therapeutics, immune evasion

                Comments

                Comment on this article

                scite_

                Similar content510

                See all similar

                Cited by3

                See all cited by

                Most referenced authors4,364

                See all reference authors