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Updated: Jul 15, 2025

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
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Dysregulation of DNAM-1-Mediated NK Cell Anti-Cancer Responses in the Tumor Microenvironment

Rossella Paolini1, Rosa Molfetta1

  • 1Department of Molecular Medicine, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, Italy.

Cancers
|September 28, 2023
PubMed

Insights

Natural killer (NK) cells fight cancer but are impaired in the tumor microenvironment. Targeting immune checkpoints like TIGIT can restore NK cell anti-tumor activity by modulating DNAM-1 receptor signaling.

Area of Science:

  • Immunology
  • Cancer Biology
  • Cellular and Molecular Medicine

Background:

  • Natural killer (NK) cells are crucial for anti-cancer immunity, utilizing activating and inhibitory receptors to target tumor cells.
  • Tumor microenvironments often suppress NK cell function by downregulating activating receptors and upregulating inhibitory checkpoints.

Purpose of the Study:

  • To review how paired co-stimulatory/inhibitory receptor recognition of PVR and Nectin2 regulates NK cell-mediated tumor cell clearance.
  • To discuss therapeutic strategies for reversing NK cell dysfunction in the tumor microenvironment.

Main Methods:

  • Review of existing literature on NK cell receptor interactions and tumor microenvironment modulation.
  • Analysis of the roles of DNAM-1, PVR, Nectin2, and TIGIT in anti-tumor immunity.

Main Results:

  • DNAM-1 receptor recognizes PVR and Nectin2, which are overexpressed on cancer cells.
  • Immune checkpoints, particularly TIGIT, can counteract DNAM-1 activation within the tumor microenvironment.
  • Targeting TIGIT shows promise for enhancing anti-tumor immune responses.

Conclusions:

  • Understanding the interplay between activating and inhibitory receptors is key to overcoming NK cell dysfunction.
  • Therapeutic targeting of immune checkpoints offers a viable strategy to restore NK cell anti-tumor activity.
Keywords:
DNAM-1 activating receptorDNAM-1 dysfunctionNK cell immune surveillancetumor microenvironment

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