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The coenzyme A precursor pantethine enhances antitumor immunity in sarcoma

The tumor microenvironment is a dynamic network of stromal, cancer, and immune cells that interact and compete for resources. We have previously identified the Vanin1 pathway as a tumor suppressor of sarcoma development via vitamin B5 and coenzyme A regeneration. Using an aggressive sarcoma cell lin...

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Autores principales: Miallot, Richard, Millet, Virginie, Roger, Anais, Fenouil, Romain, Tardivel, Catherine, Martin, Jean-Charles, Shintu, Laetitia, Berchard, Paul, Sousa Lanza, Juliane, Malissen, Bernard, Henri, Sandrine, Ugolini, Sophie, Dutour, Aurélie, Finetti, Pascal, Bertucci, François, Blay, Jean-Yves, Galland, Franck, Naquet, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10583838/
https://www.ncbi.nlm.nih.gov/pubmed/37833072
http://dx.doi.org/10.26508/lsa.202302200
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author Miallot, Richard
Millet, Virginie
Roger, Anais
Fenouil, Romain
Tardivel, Catherine
Martin, Jean-Charles
Shintu, Laetitia
Berchard, Paul
Sousa Lanza, Juliane
Malissen, Bernard
Henri, Sandrine
Ugolini, Sophie
Dutour, Aurélie
Finetti, Pascal
Bertucci, François
Blay, Jean-Yves
Galland, Franck
Naquet, Philippe
author_facet Miallot, Richard
Millet, Virginie
Roger, Anais
Fenouil, Romain
Tardivel, Catherine
Martin, Jean-Charles
Shintu, Laetitia
Berchard, Paul
Sousa Lanza, Juliane
Malissen, Bernard
Henri, Sandrine
Ugolini, Sophie
Dutour, Aurélie
Finetti, Pascal
Bertucci, François
Blay, Jean-Yves
Galland, Franck
Naquet, Philippe
author_sort Miallot, Richard
collection PubMed
description The tumor microenvironment is a dynamic network of stromal, cancer, and immune cells that interact and compete for resources. We have previously identified the Vanin1 pathway as a tumor suppressor of sarcoma development via vitamin B5 and coenzyme A regeneration. Using an aggressive sarcoma cell line that lacks Vnn1 expression, we showed that the administration of pantethine, a vitamin B5 precursor, attenuates tumor growth in immunocompetent but not nude mice. Pantethine boosts antitumor immunity, including the polarization of myeloid and dendritic cells towards enhanced IFNγ-driven antigen presentation pathways and improved the development of hypermetabolic effector CD8(+) T cells endowed with potential antitumor activity. At later stages of treatment, the effect of pantethine was limited by the development of immune cell exhaustion. Nevertheless, its activity was comparable with that of anti-PD1 treatment in sensitive tumors. In humans, VNN1 expression correlates with improved survival and immune cell infiltration in soft-tissue sarcomas, but not in osteosarcomas. Pantethine could be a potential therapeutic immunoadjuvant for the development of antitumor immunity.
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spelling pubmed-105838382023-10-19 The coenzyme A precursor pantethine enhances antitumor immunity in sarcoma Miallot, Richard Millet, Virginie Roger, Anais Fenouil, Romain Tardivel, Catherine Martin, Jean-Charles Shintu, Laetitia Berchard, Paul Sousa Lanza, Juliane Malissen, Bernard Henri, Sandrine Ugolini, Sophie Dutour, Aurélie Finetti, Pascal Bertucci, François Blay, Jean-Yves Galland, Franck Naquet, Philippe Life Sci Alliance Research Articles The tumor microenvironment is a dynamic network of stromal, cancer, and immune cells that interact and compete for resources. We have previously identified the Vanin1 pathway as a tumor suppressor of sarcoma development via vitamin B5 and coenzyme A regeneration. Using an aggressive sarcoma cell line that lacks Vnn1 expression, we showed that the administration of pantethine, a vitamin B5 precursor, attenuates tumor growth in immunocompetent but not nude mice. Pantethine boosts antitumor immunity, including the polarization of myeloid and dendritic cells towards enhanced IFNγ-driven antigen presentation pathways and improved the development of hypermetabolic effector CD8(+) T cells endowed with potential antitumor activity. At later stages of treatment, the effect of pantethine was limited by the development of immune cell exhaustion. Nevertheless, its activity was comparable with that of anti-PD1 treatment in sensitive tumors. In humans, VNN1 expression correlates with improved survival and immune cell infiltration in soft-tissue sarcomas, but not in osteosarcomas. Pantethine could be a potential therapeutic immunoadjuvant for the development of antitumor immunity. Life Science Alliance LLC 2023-10-13 /pmc/articles/PMC10583838/ /pubmed/37833072 http://dx.doi.org/10.26508/lsa.202302200 Text en © 2023 Miallot et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Miallot, Richard
Millet, Virginie
Roger, Anais
Fenouil, Romain
Tardivel, Catherine
Martin, Jean-Charles
Shintu, Laetitia
Berchard, Paul
Sousa Lanza, Juliane
Malissen, Bernard
Henri, Sandrine
Ugolini, Sophie
Dutour, Aurélie
Finetti, Pascal
Bertucci, François
Blay, Jean-Yves
Galland, Franck
Naquet, Philippe
The coenzyme A precursor pantethine enhances antitumor immunity in sarcoma
title The coenzyme A precursor pantethine enhances antitumor immunity in sarcoma
title_full The coenzyme A precursor pantethine enhances antitumor immunity in sarcoma
title_fullStr The coenzyme A precursor pantethine enhances antitumor immunity in sarcoma
title_full_unstemmed The coenzyme A precursor pantethine enhances antitumor immunity in sarcoma
title_short The coenzyme A precursor pantethine enhances antitumor immunity in sarcoma
title_sort coenzyme a precursor pantethine enhances antitumor immunity in sarcoma
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10583838/
https://www.ncbi.nlm.nih.gov/pubmed/37833072
http://dx.doi.org/10.26508/lsa.202302200
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