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The Role of IL-18 in P2RX7-Mediated Antitumor Immunity

Serena Janho Dit Hreich1,2,3, Paul Hofman2,4,5, Valérie Vouret-Craviari1,2,3

  • 1Faculty of Medicine, Université Côte d'Azur, CNRS, INSERM, IRCAN, 06108 Nice, France.

International Journal of Molecular Sciences
|June 10, 2023
PubMed

Insights

The purinergic receptor P2RX7 modulates antitumor immunity by releasing IL-18, offering a novel strategy to overcome cancer therapy resistance. Targeting this pathway may enhance current immunotherapies for improved cancer treatment outcomes.

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Cancer remains a leading cause of death globally, with treatment resistance posing a significant challenge.
  • Novel therapeutic strategies are crucial to overcome innate or acquired resistance to existing cancer therapies.
  • The purinergic receptor P2RX7 and its role in immune modulation are increasingly recognized in cancer research.

Purpose of the Study:

  • To review the role of the purinergic receptor P2RX7 in controlling tumor growth.
  • To elucidate the mechanism by which P2RX7 modulates antitumor immunity via IL-18 release.
  • To discuss the potential of targeting the P2RX7/IL-18 pathway in cancer treatment.

Main Methods:

  • Review of existing literature on P2RX7 function in cancer and immunity.
  • Analysis of ATP-induced P2RX7 activities, including cation exchange, pore opening, and inflammasome activation.
  • Examination of IL-18 production downstream of P2RX7 activation and its effect on tumor growth.

Main Results:

  • P2RX7 activation influences immune cell functions through cation exchange, large pore opening, and NLRP3 inflammasome activation.
  • P2RX7 signaling leads to the release of IL-18, a key cytokine in controlling tumor fate.
  • IL-18 production downstream of P2RX7 plays a critical role in modulating the tumor microenvironment and immune response.

Conclusions:

  • The P2RX7/IL-18 pathway is a significant regulator of antitumor immunity and tumor growth.
  • Targeting the P2RX7/IL-18 axis presents a promising therapeutic strategy for overcoming cancer resistance.
  • Combining P2RX7/IL-18 targeting with conventional immunotherapies could offer enhanced efficacy in cancer treatment.
Keywords:
IL-18P2RX7cancer

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