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Current Challenges for IDO2 as Target in Cancer Immunotherapy

Immune checkpoint inhibitors have revolutionized the clinical approach of untreatable tumors and brought a breath of fresh air in cancer immunotherapy. However, the therapeutic effects of these drugs only cover a minority of patients and alternative immunotherapeutic targets are required. Metabolism...

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Autores principales: Mondanelli, Giada, Mandarano, Martina, Belladonna, Maria Laura, Suvieri, Chiara, Pelliccia, Cristina, Bellezza, Guido, Sidoni, Angelo, Carvalho, Agostinho, Grohmann, Ursula, Volpi, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097162/
https://www.ncbi.nlm.nih.gov/pubmed/33968089
http://dx.doi.org/10.3389/fimmu.2021.679953
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author Mondanelli, Giada
Mandarano, Martina
Belladonna, Maria Laura
Suvieri, Chiara
Pelliccia, Cristina
Bellezza, Guido
Sidoni, Angelo
Carvalho, Agostinho
Grohmann, Ursula
Volpi, Claudia
author_facet Mondanelli, Giada
Mandarano, Martina
Belladonna, Maria Laura
Suvieri, Chiara
Pelliccia, Cristina
Bellezza, Guido
Sidoni, Angelo
Carvalho, Agostinho
Grohmann, Ursula
Volpi, Claudia
author_sort Mondanelli, Giada
collection PubMed
description Immune checkpoint inhibitors have revolutionized the clinical approach of untreatable tumors and brought a breath of fresh air in cancer immunotherapy. However, the therapeutic effects of these drugs only cover a minority of patients and alternative immunotherapeutic targets are required. Metabolism of l-tryptophan (Trp) via the kynurenine pathway represents an important immune checkpoint mechanism that controls adaptive immunity and dampens exaggerated inflammation. Indoleamine 2,3-dioxygenase 1 (IDO1), the enzyme catalyzing the first, rate–limiting step of the pathway, is expressed in several human tumors and IDO1 catalytic inhibitors have reached phase III clinical trials, unfortunately with disappointing results. Although much less studied, the IDO1 paralog IDO2 may represent a valid alternative as drug target in cancer immunotherapy. Accumulating evidence indicates that IDO2 is much less effective than IDO1 in metabolizing Trp and its functions are rather the consequence of interaction with other, still undefined proteins that may vary in distinct inflammatory and neoplastic contexts. As a matter of fact, the expression of IDO2 gene variants is protective in PDAC but increases the risk of developing tumor in NSCLC patients. Therefore, the definition of the IDO2 interactome and function in distinct neoplasia may open innovative avenues of therapeutic interventions.
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spelling pubmed-80971622021-05-06 Current Challenges for IDO2 as Target in Cancer Immunotherapy Mondanelli, Giada Mandarano, Martina Belladonna, Maria Laura Suvieri, Chiara Pelliccia, Cristina Bellezza, Guido Sidoni, Angelo Carvalho, Agostinho Grohmann, Ursula Volpi, Claudia Front Immunol Immunology Immune checkpoint inhibitors have revolutionized the clinical approach of untreatable tumors and brought a breath of fresh air in cancer immunotherapy. However, the therapeutic effects of these drugs only cover a minority of patients and alternative immunotherapeutic targets are required. Metabolism of l-tryptophan (Trp) via the kynurenine pathway represents an important immune checkpoint mechanism that controls adaptive immunity and dampens exaggerated inflammation. Indoleamine 2,3-dioxygenase 1 (IDO1), the enzyme catalyzing the first, rate–limiting step of the pathway, is expressed in several human tumors and IDO1 catalytic inhibitors have reached phase III clinical trials, unfortunately with disappointing results. Although much less studied, the IDO1 paralog IDO2 may represent a valid alternative as drug target in cancer immunotherapy. Accumulating evidence indicates that IDO2 is much less effective than IDO1 in metabolizing Trp and its functions are rather the consequence of interaction with other, still undefined proteins that may vary in distinct inflammatory and neoplastic contexts. As a matter of fact, the expression of IDO2 gene variants is protective in PDAC but increases the risk of developing tumor in NSCLC patients. Therefore, the definition of the IDO2 interactome and function in distinct neoplasia may open innovative avenues of therapeutic interventions. Frontiers Media S.A. 2021-04-21 /pmc/articles/PMC8097162/ /pubmed/33968089 http://dx.doi.org/10.3389/fimmu.2021.679953 Text en Copyright © 2021 Mondanelli, Mandarano, Belladonna, Suvieri, Pelliccia, Bellezza, Sidoni, Carvalho, Grohmann and Volpi https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Immunology
Mondanelli, Giada
Mandarano, Martina
Belladonna, Maria Laura
Suvieri, Chiara
Pelliccia, Cristina
Bellezza, Guido
Sidoni, Angelo
Carvalho, Agostinho
Grohmann, Ursula
Volpi, Claudia
Current Challenges for IDO2 as Target in Cancer Immunotherapy
title Current Challenges for IDO2 as Target in Cancer Immunotherapy
title_full Current Challenges for IDO2 as Target in Cancer Immunotherapy
title_fullStr Current Challenges for IDO2 as Target in Cancer Immunotherapy
title_full_unstemmed Current Challenges for IDO2 as Target in Cancer Immunotherapy
title_short Current Challenges for IDO2 as Target in Cancer Immunotherapy
title_sort current challenges for ido2 as target in cancer immunotherapy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097162/
https://www.ncbi.nlm.nih.gov/pubmed/33968089
http://dx.doi.org/10.3389/fimmu.2021.679953
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