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Extracellular ATP and P2 purinergic signalling in the tumour microenvironment

Francesco Di Virgilio1, Alba Clara Sarti2, Simonetta Falzoni2

  • 1Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy. fdv@unife.it.

Nature Reviews. Cancer
|July 15, 2018
PubMed

Insights

Extracellular ATP in the tumor microenvironment promotes cancer by suppressing immunity. Targeting the P2X7 receptor (P2X7R) with inhibitors offers a promising new strategy for effective cancer therapy.

Area of Science:

  • Biochemistry
  • Immunology
  • Oncology

Background:

  • Tumor microenvironment (TME) possesses immunosuppressive mechanisms hindering anti-tumor immunity.
  • Extracellular adenosine, generated from ATP degradation, is a potent immunosuppressive factor in the TME.
  • Extracellular ATP interacts with P2 purinergic receptors on tumor and host cells, influencing tumor progression.

Purpose of the Study:

  • To review the mechanisms by which extracellular ATP influences the TME.
  • To explore the role of P2 purinergic receptors, particularly P2X7R, in host-tumor interactions.
  • To highlight P2X7R targeting as a potential anti-cancer therapeutic strategy.

Main Methods:

  • Literature review of preclinical studies and existing research on extracellular ATP and P2 receptors in cancer.
  • Analysis of the biochemical composition and functional roles of ATP in the TME.
  • Examination of P2X7R's involvement in host-tumor cell communication and immune modulation.

Main Results:

  • Extracellular ATP is a key component of the TME, modulating host-tumor cell interactions via P2 receptors.
  • P2X7 receptor (P2X7R) is identified as a critical mediator in these interactions.
  • Preclinical data suggest P2X7R inhibition is a viable anti-cancer therapeutic approach.

Conclusions:

  • Targeting extracellular ATP's role in the TME, especially via P2X7R, presents a novel frontier in cancer therapy.
  • Small molecule inhibitors of P2X7R are under development, showing therapeutic potential.
  • Understanding ATP's multifaceted actions in the TME is crucial for designing effective cancer treatments.

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