[en] 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.
Disciplines :
Oncology
Author, co-author :
Poli, Aurélie ; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg. ; Department of Cancer Research, Luxembourg Institute of Health, Neuro-Immunology Group, Luxembourg, Luxembourg.
Oudin, Anaïs ; Department of Cancer Research, NORLUX Neuro-Oncology Laboratory, Luxembourg Institute of Health, Luxembourg, Luxembourg.
Muller, Arnaud ; Luxembourg Institute of Health, Bioinformatics Platform, Strassen, Luxembourg.
Salvato, Ilaria ; Department of Cancer Research, NORLUX Neuro-Oncology Laboratory, Luxembourg Institute of Health, Luxembourg, Luxembourg.
Scafidi, Andrea ; Department of Cancer Research, Luxembourg Institute of Health, Neuro-Immunology Group, Luxembourg, Luxembourg.
Hunewald, Oliver ; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
Domingues, Olivia; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
NAZAROV, Petr ; Luxembourg Institute of Health, Bioinformatics Platform, Strassen, Luxembourg.
Puard, Vincent ; Institut Curie Centre de Recherche, PSL Research University, RPPA platform, Paris, France.
Baus, Virginie; Department of Cancer Research, NORLUX Neuro-Oncology Laboratory, Luxembourg Institute of Health, Luxembourg, Luxembourg.
AZUAJE, Francisco ; Luxembourg Institute of Health, Bioinformatics Platform, Strassen, Luxembourg.
DITTMAR, Gunnar ; Luxembourg Institute of Health, Bioinformatics Platform, Strassen, Luxembourg.
ZIMMER, Jacques ; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
MICHEL, Tatiana ; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
MICHELUCCI, Alessandro ; Department of Cancer Research, Luxembourg Institute of Health, Neuro-Immunology Group, Luxembourg, Luxembourg.
NICLOU, Simone P. ; Department of Cancer Research, NORLUX Neuro-Oncology Laboratory, Luxembourg Institute of Health, Luxembourg, Luxembourg. ; Department of Biomedicine, University of Bergen, Bergen, Norway.
OLLERT, Markus ; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg. ; Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis, University of Southern Denmark, Odense, Denmark.
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