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The Dark Side of NK Cells in Cancer Immunotherapy

Felipe Galvez-Cancino1, Maria Armero1, David R Withers2

  • 1Laboratory of Immune-Regulation, Centre for Immuno-Oncology, Nuffield Department of Medicine, Oxford, United Kingdom.

Cancer Discovery
|September 4, 2025
PubMed

Insights

Natural killer (NK) cells can hinder cancer immunotherapy. These immune cells, while cytotoxic, may impair the effectiveness of immune checkpoint blockade through regulatory mechanisms.

Area of Science:

  • Immunology
  • Cancer Biology
  • Cellular Biology

Background:

  • Natural killer (NK) cells are innate lymphoid cells known for their cytotoxic activity against transformed cells in mice and humans.
  • NK cell infiltration into tumors is a recognized phenomenon in cancer biology.

Purpose of the Study:

  • To investigate the role of NK cell infiltration in the efficacy of immune checkpoint blockade therapies.
  • To elucidate the immune-regulatory mechanisms by which NK cells may impact cancer treatment outcomes.

Main Methods:

  • Analysis of NK cell infiltration in tumor microenvironments.
  • Assessment of NK cell function in the context of immune checkpoint blockade.
  • Investigation of immune-regulatory pathways involving NK cells.

Main Results:

  • NK cell infiltration is not universally beneficial in cancer.
  • Tumor-infiltrating NK cells can negatively regulate the anti-tumor immune response.
  • NK cells can impair the efficacy of immune checkpoint blockade treatments.

Conclusions:

  • The role of NK cells in cancer immunity is complex and context-dependent.
  • NK cell infiltration can be detrimental to the success of immune checkpoint blockade.
  • Targeting NK cell regulatory functions may represent a novel therapeutic strategy in oncology.

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