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

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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
Issue number3
Pages (from-to)682-696
Publication statusPublished - Mar 2023


  • Animals
  • Brain Neoplasms/pathology
  • Glioblastoma/genetics
  • Glioma/genetics
  • Hypersensitivity/pathology
  • Mice
  • Mice, Inbred C57BL
  • Microglia/pathology


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