Eosinophils induces glioblastoma cell suppression and apoptosis - Roles of GM-CSF and cysteinyl-leukotrienes

Int Immunopharmacol. 2023 Oct:123:110729. doi: 10.1016/j.intimp.2023.110729. Epub 2023 Aug 1.

Abstract

Background: Glioblastoma is the most common and lethal primary brain tumor in adults. Despite the available cancer treatments, the recurrence of the tumor is high, and the survival rate is low. New approaches to antitumor therapies are needed. Eosinophils are prominent in allergic diseases and accumulate in several human brain tumors. Recently, the antitumor role of eosinophils has been targeted as eosinophils release several cytotoxic factors that induce cell impairment and death.

Objective: Here we aim to evaluate the interaction of the eosinophil and glioblastoma cells, the mechanism involved in the potential killing of the glioblastoma cells by the eosinophils, and how allergy/asthma could confer a better glioblastoma prognosis.

Methods: Eosinophils and serum from asthmatic and non-asthmatic donors were cultivated with different glioblastoma cell lines.

Results: Glioblastoma cells recruit eosinophils via GM-CSF signaling, activating and increasing eosinophil survivability and function on a GM-CSF-dependent manner. Eosinophils reduce glioblastoma cells metabolism, proliferation, and migration, via Fas/FasL. Cysteinyl-leukotrienes are accounted for the asthmatic serum enhancement of the glioblastoma cell migration and proliferation. Cysteinyl-leukotrienes enhance glioblastoma cell proliferation and migration, albeit activate eosinophils that suppress glioblastoma cells.

Conclusion: Eosinophils have the potential to be key cells on glioblastoma therapeutics, as allergy and eosinophilia are correlated with a better glioblastoma prognosis. Eosinophils are elicited and attach to glioblastoma cells, where, by its cytotoxic function, via Fas/FasL, hind glioblastoma cell metabolism, proliferation, migration, and induce cell death.

Keywords: Allergy; Asthma; Cysteinyl-Leukotriene; Eosinophil; GM-CSF; Glioblastoma.

MeSH terms

  • Adult
  • Apoptosis
  • Asthma* / metabolism
  • Eosinophils / metabolism
  • Glioblastoma* / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Leukotrienes / metabolism

Substances

  • Granulocyte-Macrophage Colony-Stimulating Factor
  • cysteinyl-leukotriene
  • Leukotrienes