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Primary murine high-grade glioma cells derived from RCAS/tv-a diffuse glioma model reprogram naïve T cells into immunosuppressive regulatory T lymphocytes.

ABSTRACT: Primary murine high-grade glioma cells derived from RCAS/tv-a diffuse glioma model reprogram naïve T cells into immunosuppressive regulatory T lymphocytes.

PROVIDER: PRJNA1145333 | ENA |

REPOSITORIES: ENA

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Primary murine high-grade glioma cells derived from RCAS/tv-a diffuse glioma model reprogram naïve T cells into immunosuppressive regulatory T lymphocytes.

Project description:High-grade gliomas (HGG) and glioblastomas (GBM) are the most aggressive and lethal brain tumors. The standard of care (SOC) currently includes gross safe surgical resection followed by chemoradiotherapy. The main chemotherapeutic agents are the DNA alkylating agent Temozolomide (TMZ) and adjuvants. Due to the outdated therapeutic protocols and lack of specific treatments, there is an urgent and rising need to improve our understanding on the tumor biology and to design more effective therapeutic strategies. In vitro models are essential for investigating glioma biology and testing novel therapeutic approaches. While the use of commercially available and patient-derived glioma cell lines for in vitro studies is a common practice, they exhibit several limitations including failing to maintain genetic and phenotypic diversity of primary tumors, going through genetic drift over time, and often lacking the invasive and stem-like characteristics of patient tumors. These limitations can lead to inconsistent and non-reproducible results, hampering translational research progress. In this study, we established a novel primary murine high-grade glioma cell line, isolated from an immunocompetent HGG-bearing RCAS/t-va mouse. We characterized the transcriptome and phenotype to ensure this cell line resembles the nature of high-grade gliomas and retains the ability to reprogram primary murine T lymphocytes.

2025-08-11 | GSE274163 | GEO

Expression data from RCAS PDGFB/Nestin tv-A glioma cells within Ptprd+/+p16-/- (n=2), Ptprd+/-p16-/- (n=2), and Ptrpd-/-p16-/- (n=3) mice.

2014-06-02 | GSE55061 | GEO

Expression data from RCAS PDGFB/Nestin tv-A glioma cells within Ptprd+/+p16-/- (n=2), Ptprd+/-p16-/- (n=2), and Ptrpd-/-p16-/- (n=3) mice.

Project description:PTPRD is a tumor suppressor of glioma that is frequently co-deleted with CDKN2A/p16. We show that Ptprd and p16 cooperate to promote gliomagenesis in the RCAS PDGFB / Nestin tv-A glioma mouse model. We found unique gene expression changes within tumor cells of Ptprd+/-p16-/- vs. Ptprd+/+p16-/- and Ptprd-/-p16-/- tumor cells. Neonatal mice were injected with RCAS PDGFB GFP. At symptoms, or at 12 weeks post injection, GFP+DAPI- tumor cells were sorted for RNA extraction and hybridization on Affymetrix microarrays. The mouse strain used was a mixed background of C57/BL6 and FVB/N. Ptprd mice were from Uetani et al. 2000 and p16/Nestin-tvA mice were from Tchouganouva et al. 2007.

2014-06-02 | E-GEOD-55061 | biostudies-arrayexpress

Primary murine high-grade glioma cells derived from RCAS/tv-a diffuse glioma model reprogram naive T cells into immunosuppressive regulatory T lymphocytes.

Project description: Not available

| S-EPMC11426037 | biostudies-literature

Genetically modified IL-2 bone marrow-derived myeloid cells reprogram the glioma immunosuppressive tumor microenvironment

Project description:Low-Grade Glioma RCAs mice were treated with one dose of Vehicle (PBS) or GEMys-IL2 We analized the tumor-infiltrating immune cells at day 3 post-treatment with GEMys-IL2, or Vehicle.

2023-07-31 | GSE233646 | GEO

Effects of the Combination Therapy of a CDK4/6 and a MEK inhibitor in a Mouse Model of Diffuse Midline Glioma

Project description:Diffuse intrinsic pontine glioma (DIPG) arises in the brainstem of children, leading tumor-related death among children. A heterozygous histone H3.3K27M mutation has been shown to occur in ~80% of DIPGs, and results in brainstem gliomagenesis. There is no clinical trial for the patients with DIPG that proved to prolong survival time so far. Recently, CDK4/6 inhibitor showed feasibility and early therapeutic effect against DIPG. Also, recent research with human DIPG specimens have detected the MAPK pathway highly activated. Here, we evaluated a novel combination therapy with CDK4/6 inhibitor and MEK inhibitor to the mouse DIPG model. In order to generate DIPG‐bearing mice, we are using the RCAS/Tv‐a system, with which we are able to target specific genetic alterations in RCAS viruses (avian retroviruses) to specific cells‐of‐origin using transgenic Tv‐a‐expressing mice (Tv‐a being the receptor for RCAS viruses). We injected P3‐P5 Nestin-Tv-a;p53fl/fl mice (C56Bl/6 background) with RCAS‐PDGF‐A + RCAS‐H3.3K27M, and RCAS-Cre. The mice are treated with vehicle (methylcellurose), ribociclib as monotherapy, trametinib as monotherapy, and ribociclib and combination as combination. For short-term use, tumor tissues treated with ribociclib showed cytostatic effect, and those treated with trametinib showed cytotoxic effect, and those with combination showed both. Long-term use showed that combination therapy modestly prolonged mice survival compared with vehicle. Therefore, we need to find how DIPG showed registence to the long-term chemotherapy.

2021-09-28 | GSE184786 | GEO

Genetically modified IL-2 bone marrow-derived myeloid cells reprogram the glioma immunosuppressive tumor microenvironment

Project description:Genetically modified IL-2 bone marrow-derived myeloid cells reprogram the glioma immunosuppressive tumor microenvironment

| PRJNA977219 | ENA

Spatial transcriptomic profiling of healthy brain and RCAS-derived glioblastoma in a mouse model using 10x Genomics Visium HD

Project description:One healthy mouse brain and one glioblastoma tumor derived in the RCAS/Nestin-Tv-a mouse model were processed using the 10x Genomics Visium HD Spatial Gene Expression chemistry.

2026-03-29 | E-MTAB-16420 | biostudies-arrayexpress

Spatial transcriptomic profiling of primary and recurrent RCAS-derived glioblastoma in a mouse model using 10x Genomics Visium v1

Project description:Two primary and two post-radiotherapy recurrent glioblastoma tumors derived in the RCAS/Nestin-Tv-a mouse model were processed using the 10x Genomics Visium Spatial Gene Expression v1 chemistry.

2026-03-29 | E-MTAB-16421 | biostudies-arrayexpress

Novel cancer gene discovery using a forward genetic screen in RCAS-PDGFB driven gliomas

Project description:Here we describe the use of a high-throughput pipeline coupled to the commonly used tissue-specific retroviral RCAS-TVA mouse tumor model system. Utilizing next generation sequencing, we show that retroviral integration sites can be reproducibly detected in malignant stem cell lines generated from RCAS-PDGFB-driven glioma biopsies.

2022-07-05 | GSE207264 | GEO

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