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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1211839/full |
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| author | Iñigo Terrén Víctor Sandá Ainhoa Amarilla-Irusta Ainara Lopez-Pardo Arrate Sevilla Arrate Sevilla Gabirel Astarloa-Pando Laura Amo Laura Amo Olatz Zenarruzabeitia Luca Scorrano Luca Scorrano Francisco Borrego Francisco Borrego |
| author_facet | Iñigo Terrén Víctor Sandá Ainhoa Amarilla-Irusta Ainara Lopez-Pardo Arrate Sevilla Arrate Sevilla Gabirel Astarloa-Pando Laura Amo Laura Amo Olatz Zenarruzabeitia Luca Scorrano Luca Scorrano Francisco Borrego Francisco Borrego |
| author_sort | Iñigo Terrén |
| collection | DOAJ |
| 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 memory-like (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. |
| first_indexed | 2024-03-12T21:33:42Z |
| format | Article |
| id | doaj.art-971f7eb9bf9e468b91639e0aee251381 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T21:33:42Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-971f7eb9bf9e468b91639e0aee2513812023-07-27T15:07:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-07-011410.3389/fimmu.2023.12118391211839IL-12/15/18-induced cell death and mitochondrial dynamics of human NK cellsIñigo Terrén0Víctor Sandá1Ainhoa Amarilla-Irusta2Ainara Lopez-Pardo3Arrate Sevilla4Arrate Sevilla5Gabirel Astarloa-Pando6Laura Amo7Laura Amo8Olatz Zenarruzabeitia9Luca Scorrano10Luca Scorrano11Francisco Borrego12Francisco Borrego13Immunopathology Group, Biocruces Bizkaia Health Research Institute, Barakaldo, SpainImmunopathology Group, Biocruces Bizkaia Health Research Institute, Barakaldo, SpainImmunopathology Group, Biocruces Bizkaia Health Research Institute, Barakaldo, SpainImmunopathology Group, Biocruces Bizkaia Health Research Institute, Barakaldo, SpainImmunopathology Group, Biocruces Bizkaia Health Research Institute, Barakaldo, SpainDepartment of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country, Leioa, SpainImmunopathology Group, Biocruces Bizkaia Health Research Institute, Barakaldo, SpainImmunopathology Group, Biocruces Bizkaia Health Research Institute, Barakaldo, SpainIkerbasque, Basque Foundation for Science, Bilbao, SpainImmunopathology Group, Biocruces Bizkaia Health Research Institute, Barakaldo, SpainDepartment of Biology, University of Padova, Padova, ItalyVeneto Institute of Molecular Medicine, Padova, ItalyImmunopathology Group, Biocruces Bizkaia Health Research Institute, Barakaldo, SpainIkerbasque, Basque Foundation for Science, Bilbao, SpainNatural 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 memory-like (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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1211839/fullNK cellsmitochondriacytokine-preactivated NK cellsmemory-likecancer immunotherapyIL-12 |
| spellingShingle | Iñigo Terrén Víctor Sandá Ainhoa Amarilla-Irusta Ainara Lopez-Pardo Arrate Sevilla Arrate Sevilla Gabirel Astarloa-Pando Laura Amo Laura Amo Olatz Zenarruzabeitia Luca Scorrano Luca Scorrano Francisco Borrego Francisco Borrego IL-12/15/18-induced cell death and mitochondrial dynamics of human NK cells Frontiers in Immunology NK cells mitochondria cytokine-preactivated NK cells memory-like cancer immunotherapy IL-12 |
| title | 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_short | 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 |
| topic | NK cells mitochondria cytokine-preactivated NK cells memory-like cancer immunotherapy IL-12 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1211839/full |
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