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Natural Killer Cells Detect a Tumor-Produced Growth Factor: A Vestige of Antiviral Resistance?

Giorgio Trinchieri1

  • 1Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Trends in Immunology
|February 27, 2018
PubMed

Insights

Natural killer cells recognize stress signals like PDGF-DD via the NKp44 receptor. This interaction triggers cytokine release, offering potential for antitumor therapies.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Innate immune cells, including natural killer (NK) cells, detect pathogen-derived molecules and endogenous danger signals.
  • These endogenous ligands often indicate cellular stress or damage, alerting the immune system.
  • Receptors on innate cells mediate the recognition of these stress signals.

Purpose of the Study:

  • To identify endogenous ligands recognized by the human NKp44 receptor.
  • To investigate the functional consequences of NKp44-ligand interaction.
  • To explore the potential of this pathway in cancer immunotherapy.

Main Methods:

  • Biochemical assays to study receptor-ligand interactions.
  • Cell-based assays to measure cytokine secretion.
  • Analysis of signaling pathways involved in NK cell activation.

Main Results:

  • The study identified Platelet-Derived Growth Factor-DD (PDGF-DD) as a novel ligand for human NKp44.
  • Recognition of PDGF-DD by NKp44 represents a rare instance of a soluble growth factor acting as a stress signal.
  • Engagement of NKp44 by PDGF-DD stimulated the secretion of cytokines with antitumor properties.

Conclusions:

  • Human NKp44 recognizes the soluble growth factor PDGF-DD as a stress-associated molecule.
  • This recognition pathway activates NK cells to release cytokines that exhibit antitumor activity.
  • The NKp44-PDGF-DD axis presents a potential target for developing novel immunotherapies against cancer.

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