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Journal article
Tumor Microenvironment and Immune Escape in the Time Course of Glioblastoma
Molecular neurobiology, v 59(11), pp 6857-6873
2022
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a malignant prognosis. GBM is characterized by high cellular heterogeneity and its progression relies on the interaction with the central nervous system, which ensures the immune-escape and tumor promotion. This interplay induces metabolic, (epi)-genetic and molecular rewiring in both domains. In the present study, we aim to characterize the time-related changes in the GBM landscape, using a syngeneic mouse model of primary GBM. GL261 glioma cells were injected in the right striatum of immuno-competent C57Bl/6 mice and animals were sacrificed after 7, 14, and 21 days (7D, 14D, 21D). The tumor development was assessed through 3D tomographic imaging and brains were processed for immunohistochemistry, immunofluorescence, and western blotting. A human transcriptomic database was inquired to support the translational value of the experimental data. Our results showed the dynamic of the tumor progression, being established as a bulk at 14D and surrounded by a dense scar of reactive astrocytes. The GBM growth was paralleled by the impairment in the microglial/macrophagic recruitment and antigen-presenting functions, while the invasive phase was characterized by changes in the extracellular matrix, as shown by the analysis of tenascin C and metalloproteinase-9. The present study emphasizes the role of the molecular changes in the microenvironment during the GBM progression, fostering the development of novel multi-targeted, time-dependent therapies in an experimental model similar to the human disease.
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Details
- Title
- Tumor Microenvironment and Immune Escape in the Time Course of Glioblastoma
- Creators
- Assunta Virtuoso - University of Campania "Luigi Vanvitelli"Ciro De Luca - University of Campania "Luigi Vanvitelli"Giovanni Cirillo - University of Campania "Luigi Vanvitelli"Matteo Riva - Laboratory of Tumor Immunology and Immunotherapy, Department of Oncology, Leuven Cancer Institute, KU Leuven, 3000, Leuven, Belgium.Gabriele Romano - Drexel UniversityAngela Bentivegna - University of Milano-BicoccaMarialuisa Lavitrano - University of Milano-BicoccaMichele Papa - University of Campania "Luigi Vanvitelli"Roberto Giovannoni - University of Pisa
- Publication Details
- Molecular neurobiology, v 59(11), pp 6857-6873
- Publisher
- Springer US
- Grant note
- L.R. N.5 Bando 2003 / Regione Campania (http://dx.doi.org/10.13039/501100003852) Università degli Studi della Campania Luigi Vanvitelli PRIN 2007; PRIN 2015-2015TM24JS_009; PRIN 2017-2017XJ38A4_003; PRIN 2017-2017XJ38A4_003; PRIN 2017-2017XJ38A4_003 / Ministero dell’Istruzione, dell’Università e della Ricerca (http://dx.doi.org/10.13039/501100003407) FOE 2019; 2020 / ISBE-IT
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000849298200002
- Scopus ID
- 2-s2.0-85137229701
- Other Identifier
- 991019173715704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences