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In vivo macrophage engineering reshapes the tumor microenvironment leading to eradication of liver metastases [Visium]

ABSTRACT: In vivo macrophage engineering reshapes the tumor microenvironment leading to eradication of liver metastases [Visium]

PROVIDER: PRJNA913956 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22816622.fastq.gz	Fastqsanger.gz
	SRR22816623.fastq.gz	Fastqsanger.gz
	SRR22816624.fastq.gz	Fastqsanger.gz
	SRR22816625.fastq.gz	Fastqsanger.gz
	SRR22816626.fastq.gz	Fastqsanger.gz

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In vivo macrophage engineering reshapes the tumor microenvironment leading to eradication of liver metastases

Project description:In vivo macrophage engineering reshapes the tumor microenvironment leading to eradication of liver metastases

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In vivo macrophage engineering reshapes the tumor microenvironment leading to eradication of liver metastases [scRNA-seq]

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In vivo macrophage engineering reshapes the tumor microenvironment leading to eradication of liver metastases [scRNA-seq TCR]

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In vivo macrophage engineering reshapes the tumor microenvironment leading to eradication of liver metastases [Visium]

Project description:Liver metastases are associated with poor response to current pharmacological treatments, including immunotherapy. We describe a lentiviral vector (LV) platform to selectively engineer liver macrophages, including Kupffer cells and tumor-associated macrophages (TAMs), to deliver type I interferon (IFNα) to liver metastases. Gene-based IFNα delivery delays the growth of colorectal and pancreatic ductal adenocarcinoma liver metastases in mice. Response to IFNα is associated with TAM immune activation, enhanced MHC-II-restricted antigen presentation and reduced exhaustion of CD8+ T cells. Conversely, increased IL-10 signaling, expansion of Eomes CD4+ T cells, a cell type displaying features of type I regulatory T (Tr1) cells, and CTLA-4 expression are associated with resistance to therapy. Targeting regulatory T cell functions by combinatorial CTLA-4 immune checkpoint blockade and IFNα LV delivery expands tumor-reactive T cells, attaining complete response in most mice. These findings support a promising therapeutic strategy with feasible translation to patients with unmet medical need.

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In vivo macrophage engineering reshapes the tumor microenvironment leading to eradication of liver metastases

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

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In vivo macrophage engineering reshapes the tumor microenvironment leading to eradication of liver metastases [scRNA-seq]

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In vivo macrophage engineering reshapes the tumor microenvironment leading to eradication of liver metastases [scRNA-seq TCR]

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Fundamentals of Vaping-Associated Pulmonary Injury Leading to Severe Respiratory Distress [Visium]

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Spatially resolved transcriptomic profiling: an experimental comparison of GeoMx Digital Spatial Profiling and Visium CytAssist spatial transcriptomics in three cancer types (Chromium and Visium)

Project description:We performed Visium CytAssist (10X), GeoMx DSP (Nanostring) and Chromium Flex (10X Genomics) full transcriptome profiling on Breast Cancer (BC), Lung Cancer (LC) and diffuse large B cell lymphoma (DLBCL) samples from archival FFPE blocks. We explore the data quality across blocks with different storage times and DV200 values for all the three methods. We compared the cell type signature purity between ST methods Visium and GeoMx by utilising pathology annotations and scRNAseq. For the Visium and Chromium methods with a large number of data points we explored the heterogeneity between tissues. Finally, we demonstrate the discovery of patient-specific tumor-TME interactions across all three methods.

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