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Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Pericytes change function depending on glioblastoma vicinity: emphasis on immune regulation
Carolina Buizza1, Robert Carlsson1, Coralie Gamper1
1Department of Clinical Sciences, Translational Neurology Group, Lund University, Sweden.
Abstract:
Glioblastoma (GBM), the most aggressive brain tumor in adults, is characterized by its infiltrative growth along the perivascular space. Mural cells (MCs), encompassing pericytes and smooth muscle cells, are multifunctional perivascular cells implicated in GBM progression. MCs not only facilitate vascular co-option but have also been suggested to contribute to the immunosuppressive tumor microenvironment, promoting tumor growth and migration. However, whether MC interactions with immune cells differ based on their proximity to the tumor remains unclear. Using single-cell RNA sequencing, we analyzed MC transcriptome profiles across distinct regions relative to the tumor mass in mouse and human GBM samples. Tumor-residing MCs exhibited profound phenotypic changes, showing upregulated gene expression and enhanced signaling activity toward immune cells, with region-specific ligand-receptor interactions. Conversely, border-residing MCs, despite their abundance, showed reduced activation and lacked distinct transcriptional profiles. These findings reveal spatially defined transcriptional heterogeneity in MCs within the GBM microenvironment, underscoring their dynamic role in the GBM microenvironment. This study provides novel insights into MC responses in GBM, identifying potential avenues for targeting MC-immune-cell interactions in therapeutic interventions.
Insights
Mural cells (MCs) near glioblastoma (GBM) tumors change, signaling immune cells. Those further away show less activity, revealing spatial differences in GBM's immune interactions.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Immunology
Background:
- Glioblastoma (GBM) is an aggressive brain tumor characterized by infiltrative growth.
- Mural cells (MCs), including pericytes and smooth muscle cells, are crucial perivascular cells involved in GBM progression.
- MCs influence vascular co-option, the immunosuppressive tumor microenvironment, and tumor growth/migration.
Purpose of the Study:
- To investigate spatial differences in mural cell (MC) interactions with immune cells within the glioblastoma (GBM) microenvironment.
- To analyze the transcriptional profiles of MCs in different regions relative to the tumor mass.
Main Methods:
- Single-cell RNA sequencing was employed to analyze MC transcriptome profiles.
- Samples were obtained from distinct regions of mouse and human GBM tumors.
- Ligand-receptor interactions were assessed to understand cell-cell communication.
Main Results:
- Tumor-residing MCs displayed significant phenotypic changes, including upregulated gene expression and enhanced immune-signaling activity.
- Region-specific ligand-receptor interactions were identified between tumor MCs and immune cells.
- Border-residing MCs showed reduced activation and lacked distinct transcriptional profiles compared to tumor-residing MCs.
Conclusions:
- Spatially defined transcriptional heterogeneity exists in mural cells (MCs) within the glioblastoma (GBM) microenvironment.
- MCs play a dynamic role in the GBM microenvironment, with distinct functions based on their location.
- These findings offer potential therapeutic targets for modulating MC-immune cell interactions in GBM treatment.
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