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Multi-omic profiling of lung and liver tumor microenvironments of metastatic pancreatic cancer reveals site-specific immune-regulatory pathways [WES]

ABSTRACT: Multi-omic profiling of lung and liver tumor microenvironments of metastatic pancreatic cancer reveals site-specific immune-regulatory pathways [WES]

PROVIDER: PRJNA722019 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14239936_1.fastq.gz	Fastqsanger.gz
	SRR14239936_2.fastq.gz	Fastqsanger.gz
	SRR14239937_1.fastq.gz	Fastqsanger.gz
	SRR14239937_2.fastq.gz	Fastqsanger.gz

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Multi-omic profiling of lung and liver tumor microenvironments of metastatic pancreatic cancer reveals site-specific immune-regulatory pathways [WES]

Project description:WES was used to analyze the mutational landscape of KPC and Panc02, two murine pancreatic cancer cell lines. As expected, a relatively low mutational burden was identified in KPC cells.

2021-04-15 | GSE172105 | GEO

Multi-omic profiling of lung and liver tumor microenvironments of metastatic pancreatic cancer reveals site-specific immune-regulatory features

Project description:Multi-omic profiling of lung and liver tumor microenvironments of metastatic pancreatic cancer reveals site-specific immune-regulatory features

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Multi-omic profiling of lung and liver tumor microenvironments of metastatic pancreatic cancer reveals site-specific immune-regulatory features [RNA-seq]

Project description:Multi-omic profiling of lung and liver tumor microenvironments of metastatic pancreatic cancer reveals site-specific immune-regulatory features [RNA-seq]

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Multi-omic profiling of lung and liver tumor microenvironments of metastatic pancreatic cancer reveals site-specific immune regulatory pathways.

Project description:BackgroundThe majority of pancreatic ductal adenocarcinomas (PDAC) are diagnosed at the metastatic stage, and standard therapies have limited activity with a dismal 5-year survival rate of only 8%. The liver and lung are the most common sites of PDAC metastasis, and each have been differentially associated with prognoses and responses to systemic therapies. A deeper understanding of the molecular and cellular landscape within the tumor microenvironment (TME) metastasis at these different sites is critical to informing future therapeutic strategies against metastatic PDAC.ResultsBy leveraging combined mass cytometry, immunohistochemistry, and RNA sequencing, we identify key regulatory pathways that distinguish the liver and lung TMEs in a preclinical mouse model of metastatic PDAC. We demonstrate that the lung TME generally exhibits higher levels of immune infiltration, immune activation, and pro-immune signaling pathways, whereas multiple immune-suppressive pathways are emphasized in the liver TME. We then perform further validation of these preclinical findings in paired human lung and liver metastatic samples using immunohistochemistry from PDAC rapid autopsy specimens. Finally, in silico validation with transfer learning between our mouse model and TCGA datasets further demonstrates that many of the site-associated features are detectable even in the context of different primary tumors.ConclusionsDetermining the distinctive immune-suppressive features in multiple liver and lung TME datasets provides further insight into the tissue specificity of molecular and cellular pathways, suggesting a potential mechanism underlying the discordant clinical responses that are often observed in metastatic diseases.

| S-EPMC8118107 | biostudies-literature

Multi-omic profiling of lung and liver tumor microenvironments of metastatic pancreatic cancer reveals site-specific immune-regulatory features [RNA-seq]

Project description:To understand the site-specific differences in how metastatic pancreatic cancer is modulated, we compared the non-immune compartments by bulk RNA-seq by mouse models of lung and liver metastatic pancreatic cancer based on Kras and Trp53 driven pancreatic cancer cells (KPC).

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Project description:The spatial organization of cells within tissues is tightly linked to their biological function. Yet, methods to probe the entire transcriptome of multiple native tissue microenvironments at single cell resolution are lacking. Here, we introduce fragment-sequencing, a method that enables the transcriptomic characterization of single cells within spatially distinct tissue niches. Fragment-sequencing of the mouse metastatic liver revealed previously uncharacterized zonated genes and ligand-receptor interactions enriched in the different hepatic microenvironments and the metastatic niche.

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Multi-omic profiling of lung and liver tumor microenvironments of metastatic pancreatic cancer reveals site-specific immune-regulatory features

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

2021-04-15 | GSE172106 | GEO

Chromosome 11 analysis in myeloid malignancies - WES

Project description:Blood samples from patients with myeloid malignancies were analyzed using whole exome sequencing (WES). Data set from genotyping by microarray of the same samples has been deposited in ArrayExpress under accession number E-MTAB-1845 (https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1845/).

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RNA/WES/ATAC/scRNA sequencing of murine melanoma primary and LN metastases

Project description:The purpose of this study is to identify transcriptional, mutational, andepigenetic differences between LN metastases from primary tumors. Using in vivo serial passaging of the minimally metastatic syngeneic murine melanoma cell line B16-F0, we have generated nearly 300 unique cell lines spanning nine generations of in vivo passaging, derived from LNs, and exhibiting varying degrees of metastatic potential to LNs. Here, we perform mRNAseq on 30 of the lines representing a range of anatomical locations (distinct LNs), generations, and phylogenetic lineages. The subsequent differential expression analysis reveals a marked upregulation of immune-related genes. Additionally, we perform WES to identify differences in particular mutations, total mutational burden, and predicted neoantigen burden. Additionally, we perform ATAC-seq to assess changes in chromatin accessibility hat correlate with LN metastasis. We also perform scRNA-seq on dissociated LNs from mice with and without LN metastases.

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