Monitoring innate immune cell dynamics in the glioma microenvironment by magnetic resonance imaging and multiphoton microscopy (MR-MPM)
| Autor: | Martin Bendszus, Felix T. Kurz, Allen Alexander, Michael Platten, Frank Winkler, Michael O. Breckwoldt, Wolfgang Wick, Sabine Heiland, Matthia A. Karreman, Katrin Deumelandt, Philipp C. Münch, Kianush Karimian-Jazi, Manuel Piechutta, Manuel Fischer, Gergely Solecki, Mirco Friedrich, Kira Pfleiderer, Anna S. Berghoff |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Cell Brain tumor Medicine (miscellaneous) Tumor-associated macrophage Mice 03 medical and health sciences 0302 clinical medicine Glioma Tumor Microenvironment medicine Animals Pharmacology Toxicology and Pharmaceutics (miscellaneous) Tumor microenvironment Innate immune system Brain Neoplasms tumor-associated macrophages Chemistry Macrophages iron oxide nanoparticles Immunotherapy medicine.disease Immunity Innate immunotherapy Mice Inbred C57BL Microscopy Fluorescence Multiphoton 030104 developmental biology medicine.anatomical_structure Blood-Brain Barrier Cell Tracking 030220 oncology & carcinogenesis multiphoton microscopy Cancer research Nanoparticles Magnetic Iron Oxide Nanoparticles Microglia sense organs Preclinical imaging Research Paper MRI |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| Popis: | Rationale: Glioblastoma is the most frequent, primary brain tumor that is characterized by a highly immunosuppressive tumor microenvironment (TME). The TME plays a key role for tumor biology and the effectiveness of immunotherapies. Composition of the TME correlates with overall survival and governs therapy response. Non invasive assessment of the TME has been notoriously difficult. Methods: We have designed an in vivo imaging approach to non invasively visualize innate immune cell dynamics in the TME in a mouse glioma model by correlated MRI and multiphoton microscopy (MR-MPM) using a bimodal, fluorescently labeled iron oxide nanoparticle (NP). The introduction of Teflon cranial windows instead of conventional Titanium rings dramatically reduced susceptibility artifacts on MRI and allowed longitudinal MR-MPM imaging for innate immune cell tracking in the same animal. Results: We visualized tumor associated macrophage and microglia (TAM) dynamics in the TME and dissect the single steps of NP uptake by blood-born monocytes that give rise to tumor-associated macrophages. Next to peripheral NP-loading, we identified a second route of direct nanoparticle uptake via the disrupted blood-brain barrier to directly label tissue resident TAMs. Conclusion: Our approach allows innate immune cell tracking by MRI and multiphoton microscopy in the same animal to longitudinally investigate innate immune cell dynamics in the TME. |
| Databáze: | OpenAIRE |
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