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Targeting T-cell metabolism to boost immune checkpoint inhibitor therapy

Immune checkpoint inhibitors (ICIs) have shown promising therapeutic effects in the treatment of advanced solid cancers, but their overall response rate is still very low for certain tumor subtypes, limiting their clinical scope. Moreover, the high incidence of drug resistance (including primary and...

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Autores principales: Li, Haohao, Zhao, Alison, Li, Menghua, Shi, Lizhi, Han, Qiuju, Hou, Zhaohua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9768337/
https://www.ncbi.nlm.nih.gov/pubmed/36569893
http://dx.doi.org/10.3389/fimmu.2022.1046755
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author Li, Haohao
Zhao, Alison
Li, Menghua
Shi, Lizhi
Han, Qiuju
Hou, Zhaohua
author_facet Li, Haohao
Zhao, Alison
Li, Menghua
Shi, Lizhi
Han, Qiuju
Hou, Zhaohua
author_sort Li, Haohao
collection PubMed
description Immune checkpoint inhibitors (ICIs) have shown promising therapeutic effects in the treatment of advanced solid cancers, but their overall response rate is still very low for certain tumor subtypes, limiting their clinical scope. Moreover, the high incidence of drug resistance (including primary and acquired) and adverse effects pose significant challenges to the utilization of these therapies in the clinic. ICIs enhance T cell activation and reverse T cell exhaustion, which is a complex and multifactorial process suggesting that the regulatory mechanisms of ICI therapy are highly heterogeneous. Recently, metabolic reprogramming has emerged as a novel means of reversing T-cell exhaustion in the tumor microenvironment; there is increasing evidence that T cell metabolic disruption limits the therapeutic effect of ICIs. This review focuses on the crosstalk between T-cell metabolic reprogramming and ICI therapeutic efficacy, and summarizes recent strategies to improve drug tolerance and enhance anti-tumor effects by targeting T-cell metabolism alongside ICI therapy. The identification of potential targets for altering T-cell metabolism can significantly contribute to the development of methods to predict therapeutic responsiveness in patients receiving ICI therapy, which are currently unknown but would be of great clinical significance.
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spelling pubmed-97683372022-12-22 Targeting T-cell metabolism to boost immune checkpoint inhibitor therapy Li, Haohao Zhao, Alison Li, Menghua Shi, Lizhi Han, Qiuju Hou, Zhaohua Front Immunol Immunology Immune checkpoint inhibitors (ICIs) have shown promising therapeutic effects in the treatment of advanced solid cancers, but their overall response rate is still very low for certain tumor subtypes, limiting their clinical scope. Moreover, the high incidence of drug resistance (including primary and acquired) and adverse effects pose significant challenges to the utilization of these therapies in the clinic. ICIs enhance T cell activation and reverse T cell exhaustion, which is a complex and multifactorial process suggesting that the regulatory mechanisms of ICI therapy are highly heterogeneous. Recently, metabolic reprogramming has emerged as a novel means of reversing T-cell exhaustion in the tumor microenvironment; there is increasing evidence that T cell metabolic disruption limits the therapeutic effect of ICIs. This review focuses on the crosstalk between T-cell metabolic reprogramming and ICI therapeutic efficacy, and summarizes recent strategies to improve drug tolerance and enhance anti-tumor effects by targeting T-cell metabolism alongside ICI therapy. The identification of potential targets for altering T-cell metabolism can significantly contribute to the development of methods to predict therapeutic responsiveness in patients receiving ICI therapy, which are currently unknown but would be of great clinical significance. Frontiers Media S.A. 2022-12-07 /pmc/articles/PMC9768337/ /pubmed/36569893 http://dx.doi.org/10.3389/fimmu.2022.1046755 Text en Copyright © 2022 Li, Zhao, Li, Shi, Han and Hou 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
Li, Haohao
Zhao, Alison
Li, Menghua
Shi, Lizhi
Han, Qiuju
Hou, Zhaohua
Targeting T-cell metabolism to boost immune checkpoint inhibitor therapy
title Targeting T-cell metabolism to boost immune checkpoint inhibitor therapy
title_full Targeting T-cell metabolism to boost immune checkpoint inhibitor therapy
title_fullStr Targeting T-cell metabolism to boost immune checkpoint inhibitor therapy
title_full_unstemmed Targeting T-cell metabolism to boost immune checkpoint inhibitor therapy
title_short Targeting T-cell metabolism to boost immune checkpoint inhibitor therapy
title_sort targeting t-cell metabolism to boost immune checkpoint inhibitor therapy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9768337/
https://www.ncbi.nlm.nih.gov/pubmed/36569893
http://dx.doi.org/10.3389/fimmu.2022.1046755
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