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The emerging role of the branched chain aminotransferases, BCATc and BCATm, for anti-tumor T-cell immunity

Challenges regarding successful immunotherapy are associated with the heterogeneity of tumors and the complex interactions within the surrounding tumor microenvironment (TME), particularly those between immune and tumor cells. Of interest, T cells receive a myriad of environmental signals to elicit...

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Autores principales: Wetzel, Tanner J., Erfan, Sheila C., Ananieva, Elitsa A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9833117/
https://www.ncbi.nlm.nih.gov/pubmed/36644500
http://dx.doi.org/10.1097/IN9.0000000000000014
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author Wetzel, Tanner J.
Erfan, Sheila C.
Ananieva, Elitsa A.
author_facet Wetzel, Tanner J.
Erfan, Sheila C.
Ananieva, Elitsa A.
author_sort Wetzel, Tanner J.
collection PubMed
description Challenges regarding successful immunotherapy are associated with the heterogeneity of tumors and the complex interactions within the surrounding tumor microenvironment (TME), particularly those between immune and tumor cells. Of interest, T cells receive a myriad of environmental signals to elicit differentiation to effector subtypes, which is accompanied by metabolic reprogramming needed to satisfy the high energy and biosynthetic demands of their activated state. However, T cells are subjected to immunosuppressive signals and areas of oxygen and nutrient depletion in the TME, which causes T-cell exhaustion and helps tumor cells escape immune detection. The cytosolic and mitochondrial branched chain amino transferases, BCATc and BCATm, respectively, are responsible for the first step of the branched chain amino acid (BCAA) degradation, of which, metabolites are shunted into various metabolic processes. In recent years, BCAT isoenzymes have been investigated for their role in a variety of cancers found throughout the body; however, a gap of knowledge exists regarding the role BCAT isoenzymes play within immune cells of the TME. The aim of this review is to summarize recent findings about BCAAs and their catabolism at the BCAT step during T-cell metabolic reprogramming and to discuss the BCAT putative role in the anti-tumor immunity of T cells. Not only does this review acknowledges gaps pertaining to BCAA metabolism in the TME but it also identifies the practical application of BCAA metabolism in T cells in response to cancer and spotlights a potential target for pharmacological intervention.
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spelling pubmed-98331172023-01-12 The emerging role of the branched chain aminotransferases, BCATc and BCATm, for anti-tumor T-cell immunity Wetzel, Tanner J. Erfan, Sheila C. Ananieva, Elitsa A. Immunometabolism (Cobham) Review Challenges regarding successful immunotherapy are associated with the heterogeneity of tumors and the complex interactions within the surrounding tumor microenvironment (TME), particularly those between immune and tumor cells. Of interest, T cells receive a myriad of environmental signals to elicit differentiation to effector subtypes, which is accompanied by metabolic reprogramming needed to satisfy the high energy and biosynthetic demands of their activated state. However, T cells are subjected to immunosuppressive signals and areas of oxygen and nutrient depletion in the TME, which causes T-cell exhaustion and helps tumor cells escape immune detection. The cytosolic and mitochondrial branched chain amino transferases, BCATc and BCATm, respectively, are responsible for the first step of the branched chain amino acid (BCAA) degradation, of which, metabolites are shunted into various metabolic processes. In recent years, BCAT isoenzymes have been investigated for their role in a variety of cancers found throughout the body; however, a gap of knowledge exists regarding the role BCAT isoenzymes play within immune cells of the TME. The aim of this review is to summarize recent findings about BCAAs and their catabolism at the BCAT step during T-cell metabolic reprogramming and to discuss the BCAT putative role in the anti-tumor immunity of T cells. Not only does this review acknowledges gaps pertaining to BCAA metabolism in the TME but it also identifies the practical application of BCAA metabolism in T cells in response to cancer and spotlights a potential target for pharmacological intervention. Lippincott Williams & Wilkins 2023-01-11 /pmc/articles/PMC9833117/ /pubmed/36644500 http://dx.doi.org/10.1097/IN9.0000000000000014 Text en Copyright © 2023 The Author(s), Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by/4.0/This paper is published under Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Wetzel, Tanner J.
Erfan, Sheila C.
Ananieva, Elitsa A.
The emerging role of the branched chain aminotransferases, BCATc and BCATm, for anti-tumor T-cell immunity
title The emerging role of the branched chain aminotransferases, BCATc and BCATm, for anti-tumor T-cell immunity
title_full The emerging role of the branched chain aminotransferases, BCATc and BCATm, for anti-tumor T-cell immunity
title_fullStr The emerging role of the branched chain aminotransferases, BCATc and BCATm, for anti-tumor T-cell immunity
title_full_unstemmed The emerging role of the branched chain aminotransferases, BCATc and BCATm, for anti-tumor T-cell immunity
title_short The emerging role of the branched chain aminotransferases, BCATc and BCATm, for anti-tumor T-cell immunity
title_sort emerging role of the branched chain aminotransferases, bcatc and bcatm, for anti-tumor t-cell immunity
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9833117/
https://www.ncbi.nlm.nih.gov/pubmed/36644500
http://dx.doi.org/10.1097/IN9.0000000000000014
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