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Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma.

ABSTRACT: Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma.

PROVIDER: PRJNA895040 | ENA |

REPOSITORIES: ENA

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Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma [WES]

Project description:Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma [WES]

| PRJNA895043 | ENA

Cancer cell genetics shaping of the tumor microenvironmentreveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma [WES 2]

Project description:Cancer cell genetics shaping of the tumor microenvironmentreveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma [WES 2]

| PRJNA983703 | ENA

Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma [scRNA-Seq]

Project description:Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma [scRNA-Seq]

| PRJNA895433 | ENA

Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma [RNA-Seq]

Project description:Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma [RNA-Seq]

| PRJNA895042 | ENA

Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma.

Project description:Myeloid cells are abundant and plastic immune cell subsets in the liver, to which pro-tumorigenic, inflammatory and immunosuppressive roles have been assigned in the course of tumorigenesis. Yet several aspects underlying their dynamic alterations in hepatocellular carcinoma (HCC) progression remain elusive, including the impact of distinct genetic mutations in shaping a cancer-permissive tumor microenvironment (TME). Here, in newly generated, clinically-relevant somatic female HCC mouse models, we identify cancer genetics' specific and stage-dependent alterations of the liver TME associated with distinct histopathological and malignant HCC features. Mitogen-activated protein kinase (MAPK)-activated, NrasG12D-driven tumors exhibit a mixed phenotype of prominent inflammation and immunosuppression in a T cell-excluded TME. Mechanistically, we report a NrasG12D cancer cell-driven, MEK-ERK1/2-SP1-dependent GM-CSF secretion enabling the accumulation of immunosuppressive and proinflammatory monocyte-derived Ly6Clow cells. GM-CSF blockade curbs the accumulation of these cells, reduces inflammation, induces cancer cell death and prolongs animal survival. Furthermore, GM-CSF neutralization synergizes with a vascular endothelial growth factor (VEGF) inhibitor to restrain HCC outgrowth. These findings underscore the profound alterations of the myeloid TME consequential to MAPK pathway activation intensity and the potential of GM-CSF inhibition as a myeloid-centric therapy tailored to subsets of HCC patients.

| S-EPMC10959959 | biostudies-literature

Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma.

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

2024-02-22 | GSE216717 | GEO

Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma [WES]

Project description:Hepatocellular carcinoma (HCC) is a highly heterogenous disease associated with an equally dynamic tumor microenvironment (TME). We generated somatic HCC mouse models bearing clinically-relevant oncogenic driver combinations that faithfully recapitulated different human HCC subclasses. Using WES data, we explored the tumor mutation frequencies between models and compared them with human datasets.

2024-04-27 | GSE216716 | GEO

Cancer cell genetics shaping of the tumor microenvironmentreveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma [WES 2]

2024-02-22 | GSE234897 | GEO

Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma [scRNA-Seq]

Project description:Hepatocellular carcinoma (HCC) is a highly heterogenous disease associated with an equally dynamic tumor microenvironment (TME). We generated somatic HCC mouse models bearing clinically-relevant oncogenic driver combinations that faithfully recapitulated different human HCC subclasses. Using scRNA-seq data, we explored changes in the TME to characterize phenotypic differences between immune populations.

2024-02-22 | GSE216805 | GEO

Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma [RNA-Seq]

Project description:Hepatocellular carcinoma (HCC) is a highly heterogenous disease associated with an equally dynamic tumor microenvironment (TME). We generated somatic HCC mouse models bearing clinically-relevant oncogenic driver combinations that faithfully recapitulated different human HCC subclasses. Using RNA-seq data, we explored changes in the TME and dissected cancer cell intrinsic shapers of the TME.

2024-02-22 | GSE216715 | GEO

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