The role of microglia and P2X7 receptors in gliomas

J Neuroimmunol. 2019 Jul 15:332:138-146. doi: 10.1016/j.jneuroim.2019.04.010. Epub 2019 Apr 20.

Abstract

Gliomas are the most prevalent tumours of the central nervous system and present with high morbidity and mortality. The most common and most aggressive form of glioma is glioblastoma multiforme, of which patients have a median survival time of only 12 to 15 months. Current treatment options are limited and have a small impact on clinical outcome and prognosis. There is accumulating evidence that microglia, the immunocompetent cells of the central nervous system, and the purinergic P2X7 receptor (P2X7R) may contribute to tumour progression and pathology. Importantly, P2X7R on both tumour cells and infiltrating microglia is overexpressed in animal and human glioma cultures. Factors released by glioma cells and P2X7R activation recruit microglia into the largely immunosuppressive tumour microenvironment where they have been demonstrated to contribute to either tumour proliferation or tumour suppression. It is likely that P2X7R mediates a range of microglia effector functions in the glioma setting, potentially increasing tumour growth and proliferation. This review evaluates current evidence on the roles of microglia and P2X7R in glioma pathogenesis. Understanding the nature, mechanisms and outcomes of microglia and P2X7R activation in gliomas is necessary for the development of more therapies with increased efficacy and specificity.

Keywords: Brain tumour; Glioblastoma; Glioma; Microglia; P2X7 receptor; P2X7R.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / immunology
  • Central Nervous System Neoplasms / etiology*
  • Central Nervous System Neoplasms / immunology
  • Central Nervous System Neoplasms / pathology
  • Central Nervous System Neoplasms / therapy
  • Clonal Anergy
  • Cytokines / physiology
  • Glioma / etiology*
  • Glioma / immunology
  • Glioma / pathology
  • Glioma / therapy
  • Humans
  • Immune Tolerance
  • Matrix Metalloproteinase 2 / physiology
  • Microglia / immunology*
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / physiology*
  • Purinergic P2X Receptor Agonists / therapeutic use
  • Purinergic P2X Receptor Antagonists / adverse effects
  • Purinergic P2X Receptor Antagonists / therapeutic use
  • Rats
  • Receptors, Purinergic P2X7 / immunology
  • Receptors, Purinergic P2X7 / physiology*
  • Tumor Escape / immunology
  • Tumor Microenvironment / immunology

Substances

  • Cytokines
  • Neoplasm Proteins
  • Purinergic P2X Receptor Agonists
  • Purinergic P2X Receptor Antagonists
  • Receptors, Purinergic P2X7
  • Matrix Metalloproteinase 2