IL-12/15/18-induced cell death and mitochondrial dynamics of human NK cells

Natural killer (NK) cells are lymphocytes with potent antitumor functions and, consequently, several NK cell-based strategies have been developed for cancer immunotherapy. A remarkable therapeutic approach is the adoptive transfer of NK cells stimulated with IL-12, IL-15 and IL-18. This cytokine sti...

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Autores: Terrén Martínez, Iñigo, Sandá Mera, Víctor, Amarilla Irusta, Ainhoa, López Pardo, Ainara, Sevilla Mambrilla, Arrate, Astarloa Pando, Gabirel, Amo Herrero, Laura, Zenarruzabeitia Belaustegui, Olatz, Scorrano, Luca, Borrego Rabasco, Francisco
Formato: artículo
Fecha de publicación:2023
País:España
Recursos:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/69454
Acesso em linha:http://hdl.handle.net/10810/69454
Access Level:acceso abierto
Palavra-chave:NK cells
mitochondria
cytokine-preactivated NK cells
memory-like
cancer immunotherapy
IL-12
IL-15
IL-18
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spelling IL-12/15/18-induced cell death and mitochondrial dynamics of human NK cellsTerrén Martínez, IñigoSandá Mera, VíctorAmarilla Irusta, AinhoaLópez Pardo, AinaraSevilla Mambrilla, ArrateAstarloa Pando, GabirelAmo Herrero, LauraZenarruzabeitia Belaustegui, OlatzScorrano, LucaBorrego Rabasco, FranciscoNK cellsmitochondriacytokine-preactivated NK cellsmemory-likecancer immunotherapyIL-12IL-15IL-18Natural killer (NK) cells are lymphocytes with potent antitumor functions and, consequently, several NK cell-based strategies have been developed for cancer immunotherapy. A remarkable therapeutic approach is the adoptive transfer of NK cells stimulated with IL-12, IL-15 and IL-18. This cytokine stimulation endows NK cells with properties that resemble immunological memory and, for this reason, they are known as cytokine-induced memorylike (CIML) NK cells. Very promising results have been reported in clinical trials and yet, there are still unknown aspects of CIML NK cells. Here, we have conducted a preliminary study of their mitochondrial dynamics. Our results show that upon IL-12/15/18 stimulation the viability of NK cells decreased and an increment in mitochondrial superoxide levels was observed. In addition, we found that mitochondria appeared slightly elongated and their cristae density decreased following IL-12/15/18 stimulation, possibly in a process mediated by the low levels of optic atrophy type 1 (OPA1) protein. Interestingly, although mitophagy was slightly impaired, an increase in autophagic flux was observed, which might explain the reduced viability and the accumulation of unfit mitochondria. Our findings could be of relevance in order to design new strategies intended to improve the mitochondrial fitness of IL-12/15/18-stimulated NK cells with the aim of improving their therapeutic efficacy.The research in FB lab was supported by Fundacioı́n AECCSpanish Association Against Cancer Foundation (PROYE16074BORR) and Health Department, Basque Government (2022333018) and BBK Fundazioa (BBK22/3196). The research in LS lab was supported by Italian Cancer Research Association (AIRC) grant IG19991. IT and AA-I are recipient of a predoctoral contract funded by the Department of Education, Basque Government (PRE_2021_2_0215 and PRE_2022_1_0063). AL-P is recipient of a predoctoral contract funded by La Caixa Foundation (100010434; LCF/BQ/DI22/ 11940012). GA-P is recipient of a predoctoral contract funded by Fundacioı́n AECC-Spanish Association Against Cancer Foundation (PRDVZ21440ASTA). GA-P and AA-I are recipient of grants from Jesuı́s de Gangoiti Barrera Foundation (FJGB21/001 and FJBG21/005). AS is recipient of a grant from Margarita Salas program, for the requalification of the Spanish university system 2021-2023, financed by European Union - Next Generation EU. LA is an Ikerbasque Research Fellow and FB is an Ikerbasque Research Professor, Ikerbasque, Basque Foundation for Science.Frontiers Media202420242023info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/69454reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttps://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1211839/fullinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/© 2023 Terrén, Sandá, Amarilla-Irusta, Lopez-Pardo, Sevilla, Astarloa-Pando, Amo, Zenarruzabeitia, Scorrano and Borrego. 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.oai:addi.ehu.eus:10810/694542026-06-18T09:23:17Z
dc.title.none.fl_str_mv IL-12/15/18-induced cell death and mitochondrial dynamics of human NK cells
title IL-12/15/18-induced cell death and mitochondrial dynamics of human NK cells
spellingShingle IL-12/15/18-induced cell death and mitochondrial dynamics of human NK cells
Terrén Martínez, Iñigo
NK cells
mitochondria
cytokine-preactivated NK cells
memory-like
cancer immunotherapy
IL-12
IL-15
IL-18
title_short IL-12/15/18-induced cell death and mitochondrial dynamics of human NK cells
title_full IL-12/15/18-induced cell death and mitochondrial dynamics of human NK cells
title_fullStr IL-12/15/18-induced cell death and mitochondrial dynamics of human NK cells
title_full_unstemmed IL-12/15/18-induced cell death and mitochondrial dynamics of human NK cells
title_sort IL-12/15/18-induced cell death and mitochondrial dynamics of human NK cells
dc.creator.none.fl_str_mv Terrén Martínez, Iñigo
Sandá Mera, Víctor
Amarilla Irusta, Ainhoa
López Pardo, Ainara
Sevilla Mambrilla, Arrate
Astarloa Pando, Gabirel
Amo Herrero, Laura
Zenarruzabeitia Belaustegui, Olatz
Scorrano, Luca
Borrego Rabasco, Francisco
author Terrén Martínez, Iñigo
author_facet Terrén Martínez, Iñigo
Sandá Mera, Víctor
Amarilla Irusta, Ainhoa
López Pardo, Ainara
Sevilla Mambrilla, Arrate
Astarloa Pando, Gabirel
Amo Herrero, Laura
Zenarruzabeitia Belaustegui, Olatz
Scorrano, Luca
Borrego Rabasco, Francisco
author_role author
author2 Sandá Mera, Víctor
Amarilla Irusta, Ainhoa
López Pardo, Ainara
Sevilla Mambrilla, Arrate
Astarloa Pando, Gabirel
Amo Herrero, Laura
Zenarruzabeitia Belaustegui, Olatz
Scorrano, Luca
Borrego Rabasco, Francisco
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv NK cells
mitochondria
cytokine-preactivated NK cells
memory-like
cancer immunotherapy
IL-12
IL-15
IL-18
topic NK cells
mitochondria
cytokine-preactivated NK cells
memory-like
cancer immunotherapy
IL-12
IL-15
IL-18
description Natural killer (NK) cells are lymphocytes with potent antitumor functions and, consequently, several NK cell-based strategies have been developed for cancer immunotherapy. A remarkable therapeutic approach is the adoptive transfer of NK cells stimulated with IL-12, IL-15 and IL-18. This cytokine stimulation endows NK cells with properties that resemble immunological memory and, for this reason, they are known as cytokine-induced memorylike (CIML) NK cells. Very promising results have been reported in clinical trials and yet, there are still unknown aspects of CIML NK cells. Here, we have conducted a preliminary study of their mitochondrial dynamics. Our results show that upon IL-12/15/18 stimulation the viability of NK cells decreased and an increment in mitochondrial superoxide levels was observed. In addition, we found that mitochondria appeared slightly elongated and their cristae density decreased following IL-12/15/18 stimulation, possibly in a process mediated by the low levels of optic atrophy type 1 (OPA1) protein. Interestingly, although mitophagy was slightly impaired, an increase in autophagic flux was observed, which might explain the reduced viability and the accumulation of unfit mitochondria. Our findings could be of relevance in order to design new strategies intended to improve the mitochondrial fitness of IL-12/15/18-stimulated NK cells with the aim of improving their therapeutic efficacy.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/69454
url http://hdl.handle.net/10810/69454
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1211839/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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