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Natural Killer Cells: Tumor Surveillance and Signaling

Lizeth G Meza Guzman1,2, Narelle Keating1,2, Sandra E Nicholson1,2

  • 1The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.

Cancers
|April 16, 2020
PubMed

Insights

Natural killer (NK) cells are crucial for cancer immunotherapy. Understanding NK cell signaling pathways is key to overcoming tumor evasion and enhancing their cancer-killing potential for therapeutic benefit.

Area of Science:

  • Immunology
  • Cancer Biology
  • Cell Signaling

Background:

  • Natural killer (NK) cells are vital innate immune cells with cytotoxic capabilities against tumors.
  • NK cell activation is regulated by a balance of signals from activating and inhibitory receptors.
  • Tumors can suppress NK cell responses by altering receptor ligands and the tumor microenvironment (TME).

Purpose of the Study:

  • To review the intracellular signaling pathways governing NK cell activation and suppression.
  • To elucidate the role of signaling intermediates in NK cell-mediated cytotoxicity.
  • To identify strategies for overcoming tumor-induced immune tolerance and enhancing NK cell-based cancer therapies.

Main Methods:

  • This review synthesizes current literature on NK cell signaling.
  • Focuses on intracellular pathways and signaling intermediates.
  • Examines mechanisms of tumor immune evasion impacting NK cells.

Main Results:

  • NK cell activation thresholds are determined by the integration of signals from surface receptors.
  • Tumor cells actively modulate the TME and receptor ligand expression to inhibit NK cell function.
  • Specific intracellular signaling pathways and intermediates are critical for regulating NK cell cytotoxicity.

Conclusions:

  • A comprehensive understanding of NK cell signaling is essential for developing effective cancer immunotherapies.
  • Targeting signaling pathways could overcome tumor-induced NK cell suppression.
  • Harnessing NK cell cytotoxic potential requires breaking immune tolerance within the TME.
Keywords:
NK cellsNatural Killer cellsactivating receptorsimmune surveillanceinhibitory receptorssignaling

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