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

Publisher: Wiley-Blackwell Country of Publication: Denmark NLM ID: 7804028 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1398-9995 (Electronic) Linking ISSN: 01054538 NLM ISO Abbreviation: Allergy Subsets: MEDLINE

Publication: Copenhagen : Wiley-Blackwell
Original Publication: Copenhagen, Munksgaard.

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

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.
(© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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Keywords: T-lymphocytes; glioma-induced immunosuppression; immunoglobulin-E; microglia; tumor microenvironment

Date Created: 20221010 Date Completed: 20230306 Latest Revision: 20230309

20240829

10.1111/all.15545

36210648