Allergic airway inflammation delays glioblastoma progression and reinvigorates systemic and local immunity in mice

Aurélie Poli*, Anaïs Oudin, Arnaud Muller, Ilaria Salvato, Andrea Scafidi, Oliver Hunewald, Olivia Domingues, Petr V. Nazarov, Vincent Puard, Virginie Baus, Francisco Azuaje, Gunnar Dittmar, Jacques Zimmer, Tatiana Michel, Alessandro Michelucci, Simone P. Niclou, Markus Ollert

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

Background: Numerous patient-based studies have highlighted the protective role of immunoglobulin E-mediated allergic diseases on glioblastoma (GBM) susceptibility and prognosis. However, the mechanisms behind this observation remain elusive. Our objective was to establish a preclinical model able to recapitulate this phenomenon and investigate the role of immunity underlying such protection. Methods: An immunocompetent mouse model of allergic airway inflammation (AAI) was initiated before intracranial implantation of mouse GBM cells (GL261). RAG1-KO mice served to assess tumor growth in a model deficient for adaptive immunity. Tumor development was monitored by MRI. Microglia were isolated for functional analyses and RNA-sequencing. Peripheral as well as tumor-associated immune cells were characterized by flow cytometry. The impact of allergy-related microglial genes on patient survival was analyzed by Cox regression using publicly available datasets. Results: We found that allergy establishment in mice delayed tumor engraftment in the brain and reduced tumor growth resulting in increased mouse survival. AAI induced a transcriptional reprogramming of microglia towards a pro-inflammatory-like state, uncovering a microglia gene signature, which correlated with limited local immunosuppression in glioma patients. AAI increased effector memory T-cells in the circulation as well as tumor-infiltrating CD4+T-cells. The survival benefit conferred by AAI was lost in mice devoid of adaptive immunity. Conclusion: Our results demonstrate that AAI limits both tumor take and progression in mice, providing a preclinical model to study the impact of allergy on GBM susceptibility and prognosis, respectively. We identify a potentiation of local and adaptive systemic immunity, suggesting a reciprocal crosstalk that orchestrates allergy-induced immune protection against GBM.

Original languageEnglish
Pages (from-to)682-696
Number of pages15
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume78
Issue number3
Early online date18 Oct 2022
DOIs
Publication statusPublished - Mar 2023

Keywords

  • glioma-induced immunosuppression
  • immunoglobulin-E
  • microglia
  • T-lymphocytes
  • tumor microenvironment

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