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: Povo-Retana A, Fariñas M, Landauro-Vera R, Mojena M, Alvarez-Lucena C, Fernández-Moreno MA, Castrillo A, de la Rosa Medina JV, Sánchez-García S, Foguet C, Mas F, Marin S, Cascante M, Boscá L
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p24306
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=24306
Access Level:acceso abierto
Palabra clave:macrophages
immunometabolism
trabectedin
lurbinectedin
ROS
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spelling Immunometabolic actions of trabectedin and lurbinectedin on human macrophages: relevance for their anti-tumor activityPovo-Retana AFariñas MLandauro-Vera RMojena MAlvarez-Lucena CFernández-Moreno MACastrillo Ade la Rosa Medina JVSánchez-García SFoguet CMas FMarin SCascante MBoscá LmacrophagesimmunometabolismtrabectedinlurbinectedinROSIn 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 SA2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=24306Frontiers in ImmunologyISSN: 16643224reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p243062026-05-27T12:37:41Z
dc.title.none.fl_str_mv 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
spellingShingle Immunometabolic actions of trabectedin and lurbinectedin on human macrophages: relevance for their anti-tumor activity
Povo-Retana A
macrophages
immunometabolism
trabectedin
lurbinectedin
ROS
title_short 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_sort Immunometabolic actions of trabectedin and lurbinectedin on human macrophages: relevance for their anti-tumor activity
dc.creator.none.fl_str_mv Povo-Retana A
Fariñas M
Landauro-Vera R
Mojena M
Alvarez-Lucena C
Fernández-Moreno MA
Castrillo A
de la Rosa Medina JV
Sánchez-García S
Foguet C
Mas F
Marin S
Cascante M
Boscá L
author Povo-Retana A
author_facet Povo-Retana A
Fariñas M
Landauro-Vera R
Mojena M
Alvarez-Lucena C
Fernández-Moreno MA
Castrillo A
de la Rosa Medina JV
Sánchez-García S
Foguet C
Mas F
Marin S
Cascante M
Boscá L
author_role author
author2 Fariñas M
Landauro-Vera R
Mojena M
Alvarez-Lucena C
Fernández-Moreno MA
Castrillo A
de la Rosa Medina JV
Sánchez-García S
Foguet C
Mas F
Marin S
Cascante M
Boscá L
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv macrophages
immunometabolism
trabectedin
lurbinectedin
ROS
topic macrophages
immunometabolism
trabectedin
lurbinectedin
ROS
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.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=24306
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=24306
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv FRONTIERS MEDIA SA
publisher.none.fl_str_mv FRONTIERS MEDIA SA
dc.source.none.fl_str_mv Frontiers in Immunology
ISSN: 16643224
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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