Metabolic changes of Interleukin-12/15/18-stimulated human NK cells

Abstract Natural Killer (NK) cells acquire memory-like properties following a brief stimulation with IL-12, IL-15 and IL-18. These IL-12/15/18-preactivated NK cells, also known as cytokine-induced memory-like (CIML) NK cells, have been revealed as a powerful tool in cancer immunotherapy due to their...

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Main Authors: Iñigo Terrén, Ane Orrantia, Alba Mosteiro, Joana Vitallé, Olatz Zenarruzabeitia, Francisco Borrego
Format: Article
Language:English
Published: Nature Portfolio 2021-03-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-85960-6
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author Iñigo Terrén
Ane Orrantia
Alba Mosteiro
Joana Vitallé
Olatz Zenarruzabeitia
Francisco Borrego
author_facet Iñigo Terrén
Ane Orrantia
Alba Mosteiro
Joana Vitallé
Olatz Zenarruzabeitia
Francisco Borrego
author_sort Iñigo Terrén
collection DOAJ
description Abstract Natural Killer (NK) cells acquire memory-like properties following a brief stimulation with IL-12, IL-15 and IL-18. These IL-12/15/18-preactivated NK cells, also known as cytokine-induced memory-like (CIML) NK cells, have been revealed as a powerful tool in cancer immunotherapy due to their persistence in the host and their increased effector functions. Several studies have shown that NK cells modulate their metabolism in response to cytokine-stimulation and other stimuli, suggesting that there is a link between metabolism and cellular functions. In this paper, we have analyzed metabolic changes associated to IL-12/15/18-stimulation and the relevance of glycolytic pathway for NK cell effector functions. We have found CIML NK cells are able to retain a metabolic profile shifted towards glycolysis seven days after cytokine withdrawal. Furthermore, we found that treatment with 2-DG differently affects distinct NK cell effector functions and is stimuli-dependent. These findings may have implications in the design of NK cell-based cancer immunotherapies.
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spelling doaj.art-65ecfe7c7b8b4d3684f1ec5ff7a050c62022-12-21T20:34:25ZengNature PortfolioScientific Reports2045-23222021-03-0111111510.1038/s41598-021-85960-6Metabolic changes of Interleukin-12/15/18-stimulated human NK cellsIñigo Terrén0Ane Orrantia1Alba Mosteiro2Joana Vitallé3Olatz Zenarruzabeitia4Francisco Borrego5Immunopathology Group, Biocruces Bizkaia Health Research InstituteImmunopathology Group, Biocruces Bizkaia Health Research InstituteImmunopathology Group, Biocruces Bizkaia Health Research InstituteImmunopathology Group, Biocruces Bizkaia Health Research InstituteImmunopathology Group, Biocruces Bizkaia Health Research InstituteImmunopathology Group, Biocruces Bizkaia Health Research InstituteAbstract Natural Killer (NK) cells acquire memory-like properties following a brief stimulation with IL-12, IL-15 and IL-18. These IL-12/15/18-preactivated NK cells, also known as cytokine-induced memory-like (CIML) NK cells, have been revealed as a powerful tool in cancer immunotherapy due to their persistence in the host and their increased effector functions. Several studies have shown that NK cells modulate their metabolism in response to cytokine-stimulation and other stimuli, suggesting that there is a link between metabolism and cellular functions. In this paper, we have analyzed metabolic changes associated to IL-12/15/18-stimulation and the relevance of glycolytic pathway for NK cell effector functions. We have found CIML NK cells are able to retain a metabolic profile shifted towards glycolysis seven days after cytokine withdrawal. Furthermore, we found that treatment with 2-DG differently affects distinct NK cell effector functions and is stimuli-dependent. These findings may have implications in the design of NK cell-based cancer immunotherapies.https://doi.org/10.1038/s41598-021-85960-6
spellingShingle Iñigo Terrén
Ane Orrantia
Alba Mosteiro
Joana Vitallé
Olatz Zenarruzabeitia
Francisco Borrego
Metabolic changes of Interleukin-12/15/18-stimulated human NK cells
Scientific Reports
title Metabolic changes of Interleukin-12/15/18-stimulated human NK cells
title_full Metabolic changes of Interleukin-12/15/18-stimulated human NK cells
title_fullStr Metabolic changes of Interleukin-12/15/18-stimulated human NK cells
title_full_unstemmed Metabolic changes of Interleukin-12/15/18-stimulated human NK cells
title_short Metabolic changes of Interleukin-12/15/18-stimulated human NK cells
title_sort metabolic changes of interleukin 12 15 18 stimulated human nk cells
url https://doi.org/10.1038/s41598-021-85960-6
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AT olatzzenarruzabeitia metabolicchangesofinterleukin121518stimulatedhumannkcells
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