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Creatine supplementation enhances anti-tumor immunity by promoting adenosine triphosphate production in macrophages

Creatine is an indispensable organic compound utilized in physiological environments; however, its role in immunity is still poorly understood. Here, we show that creatine supplementation enhances anti-tumor immunity through the functional upregulation of macrophages by increasing adenosine triphosp...

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Autores principales: Peng, Zhenzi, Saito, Suguru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10471797/
https://www.ncbi.nlm.nih.gov/pubmed/37662917
http://dx.doi.org/10.3389/fimmu.2023.1176956
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author Peng, Zhenzi
Saito, Suguru
author_facet Peng, Zhenzi
Saito, Suguru
author_sort Peng, Zhenzi
collection PubMed
description Creatine is an indispensable organic compound utilized in physiological environments; however, its role in immunity is still poorly understood. Here, we show that creatine supplementation enhances anti-tumor immunity through the functional upregulation of macrophages by increasing adenosine triphosphate (ATP) production. Creatine supplementation significantly suppressed B16-F10-originated tumor growth in mice compared with the control treatment. Under these conditions, intratumor macrophages polarized towards the M1 phenotype rather than the M2 phenotype, and there was an increase in tumor antigen-specific CD8+ T cells in the mice. The cytokine production and antigen-presenting activity in the macrophages were enhanced by creatine supplementation, resulting in a substantial increase in tumor antigen-specific CD8+ T cells. ATP upregulation was achieved through the cytosolic phosphocreatine (PCr) system via extracellular creatine uptake, rather than through glycolysis and mitochondrial oxidative phosphorylation in the macrophages. Blockade of the creatine transporter (CrT) failed to upregulate ATP and enhance the immunological activity of macrophages in creatine supplementation, which also impaired CD8+ T cell activity. Consequently, CrT blockade failed to suppress tumor growth in the creatine-supplemented mice. Thus, creatine is an important nutrient that promotes macrophage function by increasing ATP levels, ultimately contributing to enhanced anti-tumor immunity orchestrated by CD8+ T cells.
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spelling pubmed-104717972023-09-02 Creatine supplementation enhances anti-tumor immunity by promoting adenosine triphosphate production in macrophages Peng, Zhenzi Saito, Suguru Front Immunol Immunology Creatine is an indispensable organic compound utilized in physiological environments; however, its role in immunity is still poorly understood. Here, we show that creatine supplementation enhances anti-tumor immunity through the functional upregulation of macrophages by increasing adenosine triphosphate (ATP) production. Creatine supplementation significantly suppressed B16-F10-originated tumor growth in mice compared with the control treatment. Under these conditions, intratumor macrophages polarized towards the M1 phenotype rather than the M2 phenotype, and there was an increase in tumor antigen-specific CD8+ T cells in the mice. The cytokine production and antigen-presenting activity in the macrophages were enhanced by creatine supplementation, resulting in a substantial increase in tumor antigen-specific CD8+ T cells. ATP upregulation was achieved through the cytosolic phosphocreatine (PCr) system via extracellular creatine uptake, rather than through glycolysis and mitochondrial oxidative phosphorylation in the macrophages. Blockade of the creatine transporter (CrT) failed to upregulate ATP and enhance the immunological activity of macrophages in creatine supplementation, which also impaired CD8+ T cell activity. Consequently, CrT blockade failed to suppress tumor growth in the creatine-supplemented mice. Thus, creatine is an important nutrient that promotes macrophage function by increasing ATP levels, ultimately contributing to enhanced anti-tumor immunity orchestrated by CD8+ T cells. Frontiers Media S.A. 2023-08-18 /pmc/articles/PMC10471797/ /pubmed/37662917 http://dx.doi.org/10.3389/fimmu.2023.1176956 Text en Copyright © 2023 Peng and Saito 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
Peng, Zhenzi
Saito, Suguru
Creatine supplementation enhances anti-tumor immunity by promoting adenosine triphosphate production in macrophages
title Creatine supplementation enhances anti-tumor immunity by promoting adenosine triphosphate production in macrophages
title_full Creatine supplementation enhances anti-tumor immunity by promoting adenosine triphosphate production in macrophages
title_fullStr Creatine supplementation enhances anti-tumor immunity by promoting adenosine triphosphate production in macrophages
title_full_unstemmed Creatine supplementation enhances anti-tumor immunity by promoting adenosine triphosphate production in macrophages
title_short Creatine supplementation enhances anti-tumor immunity by promoting adenosine triphosphate production in macrophages
title_sort creatine supplementation enhances anti-tumor immunity by promoting adenosine triphosphate production in macrophages
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10471797/
https://www.ncbi.nlm.nih.gov/pubmed/37662917
http://dx.doi.org/10.3389/fimmu.2023.1176956
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