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Dysregulated cellular functions and cell stress pathways provide critical cues for activating and targeting natural

David H Raulet1, Assaf Marcus1, Laurent Coscoy1

  • 1Department of Molecular and Cell Biology, Cancer Research Laboratory, Immunotherapy and Vaccine Research Initiative, University of California, Berkeley, Berkeley, CA, USA.

Immunological Reviews
|October 14, 2017
PubMed

Insights

Natural killer (NK) cells use activating ligands to target cancer and infected cells. Genomic damage and stress responses trigger these ligands, enhancing NK cell anti-cancer immunity.

Area of Science:

  • Immunology
  • Cell Biology
  • Cancer Biology

Background:

  • Natural killer (NK) cells are crucial for innate immunity, identifying and eliminating aberrant cells like cancer and virally infected cells.
  • NK cell effector functions are modulated by cell surface ligands and in vivo signals, such as cytokines.
  • The expression of NK-activating ligands is often linked to cellular stress and transformation.

Purpose of the Study:

  • To review the molecular pathways that regulate NK-activating ligands.
  • To explore how cellular abnormalities in cancer and infection induce these ligands.
  • To highlight the role of these pathways in NK cell-mediated immunity.

Main Methods:

  • Literature review of current research on NK cell biology, focusing on activating ligands and signaling pathways.
  • Analysis of molecular mechanisms linking cellular stress, genomic damage, and ligand expression.
  • Integration of findings related to viral infections and cancer.

Main Results:

  • Genomic damage in transformed or infected cells exposes self DNA, activating the cGAS pathway.
  • The cGAS pathway and other signaling cascades (PI-3K, integrated stress response) induce NKG2D ligands.
  • Upregulation of these ligands enhances NK cell recognition and activation against target cells.

Conclusions:

  • Cellular abnormalities provide critical signals for NK cell activation by inducing specific ligands.
  • Understanding these pathways offers insights into enhancing NK cell-based immunotherapies for cancer and infectious diseases.
  • The interplay between cellular stress, ligand expression, and NK cell function is central to immune surveillance.
Keywords:
Toll-like receptors/pattern recognition receptorscGAS-STINGcancercell stressinfectious diseasenatural killer cells

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