TY - JOUR
T1 - Tumor Microenvironment and Immune Escape in the Time Course of Glioblastoma
AU - Virtuoso, Assunta
AU - De Luca, Ciro
AU - Cirillo, Giovanni
AU - Riva, Matteo
AU - Romano, Gabriele
AU - Bentivegna, Angela
AU - Lavitrano, Marialuisa
AU - Papa, Michele
AU - Giovannoni, Roberto
N1 - Funding Information:
We thank the Fondazione Bartolo Longo III Millennio (Pompei, Naples, Italy), and Panta Rei Impresa Sociale s.r.l., Naples, Italy for the economic support to the scientific mission. A similar experimental setting with unpublished preliminary data was presented in a conference and is available as conference proceeding which can be accessed at https://www.ejh.it/index.php/ejh/article/download/3200/3070.
Funding Information:
Open access funding provided by Università degli Studi della Campania Luigi Vanvitelli within the CRUI-CARE Agreement. This work was supported by grants from Regione Campania (L.R. N.5 Bando 2003 to M.P.), the Italian Minister of Research and University (PRIN 2007 to M.P.; PRIN 2015-2015TM24JS_009 to M.P.; PRIN 2017-2017XJ38A4_003 to G.C., M.L., and M.P.): ISBE-IT FOE 2019, and 2020 to M.P.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/11
Y1 - 2022/11
N2 - 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.
AB - 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.
KW - Astrocytes
KW - FIB-2
KW - Glioma
KW - Macrophages
KW - MHCII
KW - Microglia
KW - MMP-9
KW - Neuroinflammation
KW - Spatio-temporal heterogeneity
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U2 - 10.1007/s12035-022-02996-z
DO - 10.1007/s12035-022-02996-z
M3 - Article
C2 - 36048342
AN - SCOPUS:85137229701
SN - 0893-7648
VL - 59
SP - 6857
EP - 6873
JO - Molecular Neurobiology
JF - Molecular Neurobiology
IS - 11
ER -