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Apolipoprotein A1-Manipulated Cholesterol Efflux Subverts the Phagocytic Fragility of TAMs and Improves Oncolytic Viro-Immunotherapy in Glioblastoma [TAMs RNA-seq]

ABSTRACT: We found that TAMs in the glioblatoma (GBM) tumor microenvironment are enriched for cholesterol and highly express ABCA1/G1. To investigate the biological effects of enhancing cholesterol efflux of TAMs in GBM, we constructed APOA1-overexpressing GL261 cell line. We harvested tumor tissue and sorted these TAMs by anti-mouse F4/80 magnetic beads 17 days after intracranial transplantation of GL261-APOA1 cell line and control cells in immunocompetent C57 mice. Samples were subjected to transcriptome sequencing.

ORGANISM(S): Mus musculus

PROVIDER: GSE201975 | GEO | 2022/05/04

REPOSITORIES: GEO

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Apolipoprotein A1-Manipulated Cholesterol Efflux Subverts the Phagocytic Fragility of TAMs and Improves Oncolytic Viro-Immunotherapy in Glioblastoma [BMDMs RNA-seq]

Project description:We found that TAMs in the glioblatoma (GBM) tumor microenvironment are enriched for cholesterol and highly express ABCA1/G1. To investigate the biological effects of enhancing cholesterol efflux of TAMs in GBM, we constructed APOA1-overexpressing GL261 cell line. We harvested tumor tissue and sorted these TAMs by anti-mouse F4/80 magnetic beads 17 days after intracranial transplantation of GL261-APOA1 cell line and control cells in immunocompetent C57 mice. Samples were subjected to transcriptome sequencing.

2022-10-09 | GSE214907 | GEO

Apolipoprotein A1-Manipulated Cholesterol Efflux Subverts the Phagocytic Fragility of TAMs and Improves Oncolytic Viro-Immunotherapy in Glioblastoma [Tumor RNA-seq]

Project description:We found that overexpression of APOA1 in glioblastoma (GBM) promotes cholesterol efflux from TAMs and restores phagocytosis and antigen presentation. Therefore, we constructed a recombinant oncolytic adenovirus expressing APOA1 to carry the cholesterol regulatory elements of TAMs. AdV-APOA1 exhibited better antitumor effects than AdV-Ctrl in several orthotopic GBM tumor models. Further, we collected virus-treated GL261-CAR tumors for RNA-seq to reveal differences in biological processes between them. Specifically, intracranial 14-day GL261-CAR-bearing C57BL/6J mice were i.t. injected with 1 × 108 PFU AdV-Ctrl or 1 × 108 PFU AdV-APOA1. The tumor bulks were then collected to perform transcriptome RNA-seq analysis 3 days after virus injection.

2022-05-04 | GSE201976 | GEO

Apolipoprotein A1-Manipulated Cholesterol Efflux Subverts the Phagocytic Fragility of TAMs and Improves Oncolytic Viro-Immunotherapy in Glioblastoma [TAMs RNA-seq]

Project description:Apolipoprotein A1-Manipulated Cholesterol Efflux Subverts the Phagocytic Fragility of TAMs and Improves Oncolytic Viro-Immunotherapy in Glioblastoma [TAMs RNA-seq]

| PRJNA833881 | ENA

Apolipoprotein A1-Manipulated Cholesterol Efflux Subverts the Phagocytic Fragility of TAMs and Improves Oncolytic Viro-Immunotherapy in Glioblastoma

Project description:Apolipoprotein A1-Manipulated Cholesterol Efflux Subverts the Phagocytic Fragility of TAMs and Improves Oncolytic Viro-Immunotherapy in Glioblastoma

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Apolipoprotein A1-Manipulated Cholesterol Efflux Subverts the Phagocytic Fragility of TAMs and Improves Oncolytic Viro-Immunotherapy in Glioblastoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-05-04 | GSE201977 | GEO

Apolipoprotein A1-Manipulated Cholesterol Efflux Subverts the Phagocytic Fragility of TAMs and Improves Oncolytic Viro-Immunotherapy in Glioblastoma [Tumor RNA-seq]

Project description:Apolipoprotein A1-Manipulated Cholesterol Efflux Subverts the Phagocytic Fragility of TAMs and Improves Oncolytic Viro-Immunotherapy in Glioblastoma [Tumor RNA-seq]

| PRJNA833882 | ENA

Apolipoprotein A1-Manipulated Cholesterol Efflux Subverts the Phagocytic Fragility of TAMs and Improves Oncolytic Viro-Immunotherapy in Glioblastoma [BMDMs RNA-seq]

Project description:Apolipoprotein A1-Manipulated Cholesterol Efflux Subverts the Phagocytic Fragility of TAMs and Improves Oncolytic Viro-Immunotherapy in Glioblastoma [BMDMs RNA-seq]

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Explore the transcriptomic profiles of double-positive TAMs

Project description:Several studies have described the existence of cells that co-express TAMs markers and tumor cell markers. Double-positive cells are formed by the hybridization of TAMs and GBM cells. The hybrids exhibit unique transcriptome profiles via nuclear reprogramming and contribute to GBM invasion. Another report stated that the double-positive cells are formed by the fusion of neoplastic cells and macrophages, and the fusion cells contribute to tumor heterogeneity and metastasis. However, few studies have investigated the immune regulatory functions of the double-positive cells in the GBM TME. Here, we isolated F4/80+GFP+ cells and F4/80+GFP– cells to explore the immune functions of double-positive TAMs.

2022-12-28 | GSE221777 | GEO

Tumour-associated microglia/macrophages in Glioblastoma are heterogenous and display higher immunological reactivity under aconitate decarboxylase 1 deficiency

Project description:In Glioblastoma (GBM), tumour-associated microglia/macrophages (TAMs) represent the most abundant cells of the stromal compartment contributing to tumour immune escape mechanisms. Thus, strategies targeting TAMs are emerging as promising objectives for immunotherapy. However, TAMs heterogeneity is only starting to emerge and little is known about their contribution to GBM progression. Here, we comprehensively study the molecular changes of TAMs in the GL261 GBM mouse model by single-cell RNA-sequencing across GBM progression and in the absence of Acod1/Irg1, a key gene involved in macrophage metabolic reprogramming. We identify distinct TAM profiles, mainly based on their ontogeny, which recapitulate microglia- versus macrophage-like features showing key transcriptional differences and rapidly adapting along GBM stages. Notably, we uncover a decreased antigen-presenting cell signature in TAMs along tumour progression that is less prominent in Acod1/Irg1-deficient mice. Overall, our results provide insights into TAMs heterogeneity and highlight a potential role for Acod1/Irg1 in TAMs polarization along GBM progression.

2020-09-16 | GSE158016 | GEO

Gene expression profiles of tumor-associated macrophages (TAMs) overexpressing miR-511-3p

Project description:Hematopoietic stem/progenitor cells (HS/PCs) were transduced with lentiviral vectors overexpressing OFP and either miR-511-3p or a control, mutated miRNA sequence (miR-511-3p-mut). The transduced HS/PCs were then transplanted in recipient C57BL/6 mice. Tumors (Lewis lung carcinomas, LLC) were injected s.c. 4 weeks after HS/PC transplant. Lentiviral vector-transduced (OFP+), tumor-associated macrophages (TAMs) were isolated 4 weeks after LLC injection by fluorescence-activated cell sorting. Gene expression profiles of TAMs overexpressing either miR-511-3p or miR-511-3p-mut were obtained from 3 independent biological samples/each. Gene expression profiles of miRNA-overexpressing TAMs were then compared with the gene expression profiles of wild-type TAMs isolated from LLCs grown in nontransplanted C57BL/6 mice; the latter TAMs were subfractioned into MRC1+CD11c(low) or CD11c+MRC1(low) subsets before RNA isolation and analysis. Comparison of gene expression profiles of TAMs revealed that miR-511-3p overexpression tunes down the expression of multiple genes that are classically upregulated in protumoral MRC1+CD11c(low) TAMs. TAMs were isolated from Lewis lung carcinomas grown s.c. in C57BL/6 mice.

2012-04-01 | E-GEOD-34903 | biostudies-arrayexpress

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