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Immunometabolic actions of trabectedin and lurbinectedin on human macrophages: relevance for their anti-tumor activity

In recent years, the central role of cell bioenergetics in regulating immune cell function and fate has been recognized, giving rise to the interest in immunometabolism, an area of research focused on the interaction between metabolic regulation and immune function. Thus, early metabolic changes ass...

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Autores principales: Povo-Retana, Adrián, Fariñas, Marco, Landauro-Vera, Rodrigo, Mojena, Marina, Alvarez-Lucena, Carlota, Fernández-Moreno, Miguel A., Castrillo, Antonio, de la Rosa Medina, Juan Vladimir, Sánchez-García, Sergio, Foguet, Carles, Mas, Francesc, Marin, Silvia, Cascante, Marta, Boscá, Lisardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10479946/
https://www.ncbi.nlm.nih.gov/pubmed/37675104
http://dx.doi.org/10.3389/fimmu.2023.1211068
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author Povo-Retana, Adrián
Fariñas, Marco
Landauro-Vera, Rodrigo
Mojena, Marina
Alvarez-Lucena, Carlota
Fernández-Moreno, Miguel A.
Castrillo, Antonio
de la Rosa Medina, Juan Vladimir
Sánchez-García, Sergio
Foguet, Carles
Mas, Francesc
Marin, Silvia
Cascante, Marta
Boscá, Lisardo
author_facet Povo-Retana, Adrián
Fariñas, Marco
Landauro-Vera, Rodrigo
Mojena, Marina
Alvarez-Lucena, Carlota
Fernández-Moreno, Miguel A.
Castrillo, Antonio
de la Rosa Medina, Juan Vladimir
Sánchez-García, Sergio
Foguet, Carles
Mas, Francesc
Marin, Silvia
Cascante, Marta
Boscá, Lisardo
author_sort Povo-Retana, Adrián
collection PubMed
description In recent years, the central role of cell bioenergetics in regulating immune cell function and fate has been recognized, giving rise to the interest in immunometabolism, an area of research focused on the interaction between metabolic regulation and immune function. Thus, early metabolic changes associated with the polarization of macrophages into pro-inflammatory or pro-resolving cells under different stimuli have been characterized. Tumor-associated macrophages are among the most abundant cells in the tumor microenvironment; however, it exists an unmet need to study the effect of chemotherapeutics on macrophage immunometabolism. Here, we use a systems biology approach that integrates transcriptomics and metabolomics to unveil the immunometabolic effects of trabectedin (TRB) and lurbinectedin (LUR), two DNA-binding agents with proven antitumor activity. Our results show that TRB and LUR activate human macrophages toward a pro-inflammatory phenotype by inducing a specific metabolic rewiring program that includes ROS production, changes in the mitochondrial inner membrane potential, increased pentose phosphate pathway, lactate release, tricarboxylic acids (TCA) cycle, serine and methylglyoxal pathways in human macrophages. Glutamine, aspartate, histidine, and proline intracellular levels are also decreased, whereas oxygen consumption is reduced. The observed immunometabolic changes explain additional antitumor activities of these compounds and open new avenues to design therapeutic interventions that specifically target the immunometabolic landscape in the treatment of cancer.
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spelling pubmed-104799462023-09-06 Immunometabolic actions of trabectedin and lurbinectedin on human macrophages: relevance for their anti-tumor activity Povo-Retana, Adrián Fariñas, Marco Landauro-Vera, Rodrigo Mojena, Marina Alvarez-Lucena, Carlota Fernández-Moreno, Miguel A. Castrillo, Antonio de la Rosa Medina, Juan Vladimir Sánchez-García, Sergio Foguet, Carles Mas, Francesc Marin, Silvia Cascante, Marta Boscá, Lisardo Front Immunol Immunology In recent years, the central role of cell bioenergetics in regulating immune cell function and fate has been recognized, giving rise to the interest in immunometabolism, an area of research focused on the interaction between metabolic regulation and immune function. Thus, early metabolic changes associated with the polarization of macrophages into pro-inflammatory or pro-resolving cells under different stimuli have been characterized. Tumor-associated macrophages are among the most abundant cells in the tumor microenvironment; however, it exists an unmet need to study the effect of chemotherapeutics on macrophage immunometabolism. Here, we use a systems biology approach that integrates transcriptomics and metabolomics to unveil the immunometabolic effects of trabectedin (TRB) and lurbinectedin (LUR), two DNA-binding agents with proven antitumor activity. Our results show that TRB and LUR activate human macrophages toward a pro-inflammatory phenotype by inducing a specific metabolic rewiring program that includes ROS production, changes in the mitochondrial inner membrane potential, increased pentose phosphate pathway, lactate release, tricarboxylic acids (TCA) cycle, serine and methylglyoxal pathways in human macrophages. Glutamine, aspartate, histidine, and proline intracellular levels are also decreased, whereas oxygen consumption is reduced. The observed immunometabolic changes explain additional antitumor activities of these compounds and open new avenues to design therapeutic interventions that specifically target the immunometabolic landscape in the treatment of cancer. Frontiers Media S.A. 2023-08-22 /pmc/articles/PMC10479946/ /pubmed/37675104 http://dx.doi.org/10.3389/fimmu.2023.1211068 Text en Copyright © 2023 Povo-Retana, Fariñas, Landauro-Vera, Mojena, Alvarez-Lucena, Fernández-Moreno, Castrillo, de la Rosa Medina, Sánchez-García, Foguet, Mas, Marin, Cascante and Boscá 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
Povo-Retana, Adrián
Fariñas, Marco
Landauro-Vera, Rodrigo
Mojena, Marina
Alvarez-Lucena, Carlota
Fernández-Moreno, Miguel A.
Castrillo, Antonio
de la Rosa Medina, Juan Vladimir
Sánchez-García, Sergio
Foguet, Carles
Mas, Francesc
Marin, Silvia
Cascante, Marta
Boscá, Lisardo
Immunometabolic actions of trabectedin and lurbinectedin on human macrophages: relevance for their anti-tumor activity
title Immunometabolic actions of trabectedin and lurbinectedin on human macrophages: relevance for their anti-tumor activity
title_full Immunometabolic actions of trabectedin and lurbinectedin on human macrophages: relevance for their anti-tumor activity
title_fullStr Immunometabolic actions of trabectedin and lurbinectedin on human macrophages: relevance for their anti-tumor activity
title_full_unstemmed Immunometabolic actions of trabectedin and lurbinectedin on human macrophages: relevance for their anti-tumor activity
title_short Immunometabolic actions of trabectedin and lurbinectedin on human macrophages: relevance for their anti-tumor activity
title_sort immunometabolic actions of trabectedin and lurbinectedin on human macrophages: relevance for their anti-tumor activity
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10479946/
https://www.ncbi.nlm.nih.gov/pubmed/37675104
http://dx.doi.org/10.3389/fimmu.2023.1211068
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