Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Glutaminase inhibition impairs CD8 T cell activation in STK11/Lkb1 deficient lung cancer

ABSTRACT: To characterize the impact of KRAS co-mutations KEAP1 and STK11/Lkb1 on the metabolic and immune microenvironment of lung adenocarcinoma in immune-intact models, we generated a cohort of genetically engineered mouse models (GEMMs) to reflect the diverse tumor suppressor landscape seen in patients. Mice carrying the KrasG12D allele (K)21 were crossed with Keap1flox/flox (KK)22 and/or Lkb1flox/flox (KKL, KL)23 mice and genetic recombination induced by intranasal inhalation of Ad5-CMV-Cre adenovirus. We interrogated the metabolites present in lung tumor nodules collected from cohorts of KK, KL and KKL mice.

ORGANISM(S): Mouse Mus Musculus

TISSUE(S): Lung

DISEASE(S): Cancer

SUBMITTER: Best Sarah

PROVIDER: ST002066 | MetabolomicsWorkbench | Tue Jan 18 00:00:00 GMT 2022

REPOSITORIES: MetabolomicsWorkbench

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	mwtab	Other

Items per page:

1 - 1 of 1

Similar Datasets

Targeting focal adhesion kinase boosts immune response in KRAS/LKB1 co-mutated lung adenocarcinoma via remodeling the tumor microenvironment

Project description:Background: KRAS mutation is one of the most common oncogenic drivers in NSCLC, however, the response to immunotherapy is heterogeneous owing to the distinct co-occurring genomic alterations. KRAS/LKB1 co-mutated lung adenocarcinoma displays poor response to PD-1 blockade whereas the mechanism remains undetermined. Methods: We explored the specific characteristics of tumor microenvironment (TME) in KL tumors using syngeneic KRASG12DLKB1-/-(KL) and KRASG12DTP53-/- (KP) lung cancer mouse models. The impact of focal adhesion kinase (FAK) inhibitor on KL lung tumors was investigated in vitro and in vivo through evaluation of both KL cell lines and KL lung cancer mouse models. Results: We identified KL tumors as “immune-cold” tumors with excessive extracellular matrix (ECM) collagen deposition that formed a physical barrier to block the infiltration of CD8+T cells. Mechanistically, abundant activated cancer-associated fibroblasts (CAFs) resulted from FAK activation contributed to the formation of the unique TME of KL tumors. FAK inhibition with a small molecular inhibitor could remodel the TME by inhibiting CAFs activation, decreasing collagen deposition and further facilitating the infiltration of anti-tumor immune cells, including CD8+ T cells, DC cells and M1-like macrophages into tumors, hence, converting “immune-cold” KL tumors into “immune-hot” tumors. The combined FAK inhibitor and PD-1 blockade therapy synergistically retarded primary and metastatic tumor growth of KL tumors.Conclusions: Our study identified FAK as a promising intervention target for KL tumors and provided basis for the combination of FAK inhibitor with PD-1 blockade in the management of KL lung cancers.

2024-02-07 | GSE244452 | GEO

MicroRNA profile of tumorigenic cells during formation of pulmonary adenocarcinoma

Project description:Study designed to obtain microRNA profile of tumorigenic Sca-1+CD34+ cells during the formation of pulmonary adenocarcinoma. After intranasal infection with adenovirus CRE (Ad-Cre), lung adenocarcinoma was identified pathologically in Lox-stop-lox Kras (LSL-Kras) G12D mice. Sca-1+CD34+ cells were sorted by flow cytometry and tested for the tumor-initiating ability to undergo self-renewal and differentiation. MiRNA profile was obtained from the microarray and further confirmed by qRT-PCR.The function of miRNAs was predicted bioinformatically, and miR-294 was verified to explore its relationship with tumor migration and invasion.

2014-08-02 | GSE60001 | GEO

Expression data from mouse lung squamous cell carcinoma isolated from KrasG12D;Lkb1 mice treated with Vehicle or with catalytic mTOR inhibitor MLN128 for 8 weeks

Project description:Lung tumors were induced in Kras LSL-G12D; Lkb1 fl/fl mice by intranasal inhalation of Adenoviral Cre. Four weeks after tumor induction, mice were randomly assigned into two groups and treated daily with either Vehicle or 1mg/kg MLN128 for 8 weeks. At the end of the study, mice were euthanized and tumors were dissected out from lung and snap frozen in liquid nitrogen. Frozen tumors were stored in -80C freezer. Lung squamous cell carcinomas adapted to chronic treatement with MLN128 We used microarrays to examine changes in the gene expression in pathways that allowed MLN128 treated squamous cell carcinomas to continue to proliferate in the presence of MLN128

2018-02-06 | GSE110108 | GEO

ChIP sequencing of BACH1 in mTC and mTN cells

Project description:The goal of the study is to define the impact of long-term administration of antioxidants on lung cancer progression. mTC and mTN cell lines were established from mice with KrasG12D/+ lung tumors 58 weeks post intranasal Cre-delivery. mTC cells comes from control mice, mTN cells come from NAC-treated mice. Mice were maintained on a mixed C57BL/6-129/Sv genetic background

2019-07-02 | GSE128180 | GEO

RNA sequencing of mTC and mTN cells

2019-07-02 | GSE128153 | GEO

Expression data comparing the effect of IKK2 KO on a KRAS mouse model

Project description:Given that the NF-κB pathway plays an important role in tumor development and that IKK2 is the seminal kinase responsible for NF-κB pathway activation, we were particularly interested in exploring the therapeutic potential of IKK2 inhibition in non-small cell lung cancers. We crossed IKK2fl/fl and KrasG12D mice so that we could simultaneously activate KrasG12D to initiate tumor formation and inactivate IKK2, upon transduction by Cre lentiviral vectors. RNA isolated from finely dissected tumor nodules and tumor cell lines (4A3 and1D3) was applied to microarray analysis using Affymetrix Mouse Gene 1.0 STArrays according to the manufacturer’s instructions.

2011-12-15 | E-GEOD-30049 | biostudies-arrayexpress

Effect of Omomyc in vivo treatment on lung adenocarcinoma of KRasLSL-G12D/+ transgenic mouse

Project description:Analysis of Kras-driven lung adenocarcinoma of mice intranasally treated with 2.37 mg/kg Omomyc or vehicle (10 mM sodium acetate pH 6.5) for three days. KRasLSL-G12D/+ mice were treated with Omomyc by intranasal administration sixteen weeks after Adeno-Cre infection. Mice (n=2 for vehicle treated and n=3 for Omomyc treated group) were euthanized three days post-treatment and lung tumors were excised and frozen at -80ºC until processing.

2019-04-01 | GSE126452 | GEO

Global evolution of the tumor microenvironment associated with progression from preinvasive/minimally invasive to invasive human lung adenocarcinoma

Project description:To investigate changes in the tumor microenvironment (TME) during lung cancer progression, we interrogate tumors from two computer tomography (CT) defined groups. Pure non-solid (pNS) CT density nodules contain preinvasive/minimally invasive cancers and solid density nodules invasive cancers. Profiling data reveal a dynamic interaction between the tumor and its TME throughout progression. Alterations in genes regulating the extracellular matrix and genes regulating fibroblasts are central at the preinvasive state. T cell-mediated immune suppression is initiated in preinvasive nodules and sustained with rising intensity through progression to invasive tumors. Reduced T cell infiltration of the cancer cell nests is more frequently associated with preinvasive cancers, possibly until tumor evolution leads to a durable, viable invasive phenotype accompanied by more varied and robust immune suppression. Upregulation of immune checkpoints occurs only in the invasive nodules. Throughout progression an effector immune response is present but is effectively thwarted by the immune-suppressive elements.

2022-04-10 | GSE193725 | GEO

Deciphering the immunopeptidome in vivo reveals novel tumor antigens

Project description:Effective immunosurveillance of cancer requires the presentation of peptide antigens on major histocompatibility complex Class I (MHC-I). Recent developments in proteomics have improved the identification of peptides that are naturally presented by MHC-I, collectively known as the “immunopeptidome”. Current approaches to profile tumor immunopeptidomes have been limited to in vitro investigation, which fails to capture the in vivo repertoire of MHC-I peptides, or bulk tumor lysates, which are obscured by the lack of cancer cell-specific MHC-I isolation. To overcome these limitations, we report here the engineering of a Cre recombinase-inducible affinity tag into the endogenous mouse MHC-I gene and targeting of this allele to the KrasLSL-G12D/+; p53fl/fl (KP) mouse model (KP/KbStrep). This novel approach has allowed us to precisely isolate MHC-I peptides from autochthonous pancreatic ductal adenocarcinoma (PDAC) and lung adenocarcinoma (LUAD) in vivo. With this powerful analytical tool, we were able to profile the evolution of the LUAD immunopeptidome from the alveolar type 2 cell-of-origin through late-stage disease. Differential peptide presentation in LUAD is not driven by increased mRNA expression or translation rate and is likely driven by post-translational mechanisms. Vaccination of mice with peptides presented by LUAD in vivo provoked CD8 T-cell responses in naïve and tumor bearing mice. Many peptides unique to LUAD, including immunogenic peptides, exhibited very low expression of the cognate mRNA provoking reconsideration of antigen prediction pipelines that triage peptides according to transcript abundance. Beyond cancer, the KbStrep allele is compatible with a broad range of Cre-driver lines to explore antigen presentation in vivo in the pursuit of understanding basic immunology, infectious disease, and autoimmunity.

2022-06-20 | PXD033232 | Pride

Detecting metastatic tumors after γ-irradiation using longitudinal molecular imaging and gene expression profiling of metastatic tumor nodules

Project description:Microarray analysis in the mouse metastatic tumor after ɣ-irradiation(ɣ-IR): non-irradiated primary tumor vs. radiated primary tumor vs. metastatic tumor after ɣ-irradiation Metastatic tumors in C6-L (rat glioma cells ) xenografted mice were studied after local treatment with fractionated γ-IR. To accurately detect the metastatic nodules after γ-IR, we observed the effect of γ-IR on distant metastatic tumor growth. Metastatic nodules after γ-IR indicated extensive colonization of C6-L cells in the lungs within 6 weeks after γ-IR. Identified and described the molecular events occurring after γ-IR through gene expression profiling to elucidate genetic changes (differentially expressed genes between the γ-IR primary tumors vs. non-γ-IR primary tumors and metastatic lung nodules vs. γ-IR primary tumors). We investigated the change of gene expression profile in the γ-IR primary tumors vs. non-γ-IR primary tumors and metastatic lung nodules vs. γ-IR primary tumors in rat glioma (C6-L cell) xenograft model.

2015-09-18 | E-GEOD-73116 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data