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Targeting NKG2D and NKp30 Ligands Shedding to Improve NK Cell-Based Immunotherapy

Alessandra Zingoni1, Elisabetta Vulpis1, Ilaria Nardone1

  • 1Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.

Critical Reviews in Immunology
|August 29, 2017
PubMed

Insights

Tumors evade natural killer (NK) cell detection by shedding activating ligands. Targeting metalloproteinases that cleave these ligands may restore NK cell antitumor responses.

Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Biology

Background:

  • Natural killer (NK) cells are crucial for antitumor immunity, recognizing cancer cells via activating receptors.
  • Tumors employ immune escape strategies, including downregulating NK cell ligands through proteolytic shedding.
  • Key NK cell activating receptors NKG2D and NKp30 ligands (MICA/B, ULBPs, B7-H6) are shed by cancer cells.

Purpose of the Study:

  • To examine the shedding of NKG2D and NKp30 ligands by cancer cells.
  • To investigate how cancer therapy modulates this ligand shedding process.
  • To discuss targeting metalloproteinases for novel cancer immunotherapies.

Main Methods:

  • Analysis of NK cell activating receptor-ligand interactions.
  • Investigation of proteolytic shedding mechanisms mediated by metalloproteinases.
  • Evaluation of ligand shedding in response to cancer treatments.

Main Results:

  • Cancer cells shed NKG2D and NKp30 ligands via metalloproteinase activity, facilitating immune evasion.
  • Cancer therapy can influence the rate of ligand shedding.
  • Metalloproteinases play a significant role in NK cell immune escape.

Conclusions:

  • Targeting metalloproteinases involved in ligand shedding offers a potential strategy to enhance NK cell-mediated antitumor immunity.
  • Interfering with ligand shedding could overcome tumor immune escape mechanisms.
  • This approach may lead to novel therapeutic schemes against cancer.

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