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Updated: Jul 19, 2025

Analysis of Human Natural Killer Cell Metabolism
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Analysis of Human Natural Killer Cell Metabolism

Published on: June 22, 2020

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

Iñigo Terrén1, Víctor Sandá1, Ainhoa Amarilla-Irusta1

  • 1Immunopathology Group, Biocruces Bizkaia Health Research Institute, Barakaldo, Spain.

Frontiers in Immunology
|August 14, 2023
PubMed

Insights

Cytokine-induced memory-like (CIML) NK cells show reduced viability and impaired mitochondrial function after IL-12/15/18 stimulation. This study investigates mitochondrial dynamics and autophagic flux in CIML NK cells for improved cancer immunotherapy.

Area of Science:

  • Immunology
  • Cell Biology
  • Cancer Research

Background:

  • Natural killer (NK) cells are crucial for antitumor immunity.
  • Adoptive transfer of IL-12, IL-15, and IL-18-stimulated NK cells creates cytokine-induced memory-like (CIML) NK cells with therapeutic potential.
  • The mitochondrial dynamics of CIML NK cells remain largely unexplored.

Purpose of the Study:

  • To investigate the mitochondrial dynamics of CIML NK cells following IL-12/15/18 stimulation.
  • To explore the impact of cytokine stimulation on NK cell viability, mitochondrial function, and autophagic processes.

Main Methods:

  • NK cells were stimulated with IL-12, IL-15, and IL-18.
  • Mitochondrial superoxide levels, morphology, and cristae density were assessed.
  • Levels of optic atrophy type 1 (OPA1) protein were analyzed.
  • Mitophagy and autophagic flux were evaluated.

Main Results:

  • IL-12/15/18 stimulation decreased NK cell viability and increased mitochondrial superoxide levels.
  • Mitochondria showed slight elongation and decreased cristae density, potentially linked to reduced OPA1 protein.
  • Autophagic flux increased, while mitophagy was slightly impaired, contributing to reduced viability and accumulation of dysfunctional mitochondria.

Conclusions:

  • Cytokine stimulation induces significant alterations in NK cell mitochondrial dynamics and autophagic pathways.
  • These changes may compromise CIML NK cell fitness and therapeutic efficacy.
  • Further research into enhancing mitochondrial fitness is warranted to optimize CIML NK cell-based cancer immunotherapies.
Keywords:
IL-12IL-15IL-18NK cellscancer immunotherapycytokine-preactivated NK cellsmemory-likemitochondria

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