Cancer-derived extracellular vesicles in natural killer cell immune evasion: Molecular mechanisms and therapeutic

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Updated: Sep 19, 2025

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Elaina Coleborn1, Raluca Ghebosu2, Joy Wolfram3

  • 1Frazer Institute, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, QLD 4102, Australia.

Molecular Therapy : the Journal of the American Society of Gene Therapy
|June 2, 2025
PubMed

Insights

Cancer cells release extracellular vesicles that suppress natural killer (NK) cells, hindering cancer immunosurveillance. This review explores NK cell suppression by cancer extracellular vesicles and therapeutic strategies.

Area of Science:

  • Immunology
  • Cancer Biology
  • Cell Biology

Background:

  • Natural killer (NK) cells are crucial innate immune cells for identifying and eliminating cancer cells.
  • Cancer cells exploit extracellular vesicles (EVs) to create an immunosuppressive tumor microenvironment, impairing NK cell function.
  • Cancer-derived EVs suppress NK cell activity by inhibiting cytolytic proteins and downregulating key receptors.

Purpose of the Study:

  • To review the current understanding of interactions between cancer-derived EVs and NK cells.
  • To elucidate the mechanisms by which EVs induce NK cell immunosuppression.
  • To discuss the implications for developing novel cancer immunotherapies targeting NK cell dysfunction.

Main Methods:

  • Literature review of studies investigating cancer-EVs and NK cell interactions.
  • Analysis of mechanisms underlying NK cell dysfunction induced by cancer EVs.
  • Synthesis of information on therapeutic strategies to restore NK cell anti-tumor activity.

Main Results:

  • Cancer-derived EVs impair NK cell-mediated killing, survival, proliferation, migration, and metabolism.
  • EVs from various cancer types (e.g., leukemia, melanoma, lung, breast) exhibit immunosuppressive properties.
  • NK cell suppression by EVs represents a significant barrier to effective cancer immunosurveillance.

Conclusions:

  • Cancer-derived EVs are potent mediators of immune suppression, specifically targeting NK cells.
  • Targeting EV-mediated NK cell suppression offers a promising avenue for enhancing cancer immunotherapy.
  • Further research is needed to fully understand these interactions and develop effective therapeutic interventions.
Keywords:
exosomesimmunoevasionimmunosuppressioninnate immunityintercellular communicationtumor microenvironment

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