Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Immune effector monocyte - neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer

ABSTRACT: Metastatic behaviour varies significantly among breast cancers. Mechanisms explaining why the majority of breast cancer patients never develop metastatic outgrowth are largely lacking but could underlie the development of novel immunotherapeutic target molecules. Here we show interplay between non-metastatic primary breast cancer and innate immune response, acting together to control metastatic progression. The primary tumor systemically recruits IFNγ-producing immune effector monocytes to the lung. IFNγ upregulates Tmem173/STING in neutrophils and enhances their killing capacity. The immune effector monocytes and tumoricidal Tmem173/STINGhigh neutrophils target disseminated tumor cells in the lungs, preventing metastatic outgrowth. Importantly, our findings could underlie the development of immunotherapeutic target molecules that augment the function of immune effector monocytes and Tmem173high neutrophils.

ORGANISM(S): Mus musculus

PROVIDER: GSE137300 | GEO | 2019/09/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

scRNAseq of the bone marrow immune microenvironment in control and 5TGM1 myeloma-bearing C57Bl/6 and KaLwRij mice

Project description:We hypothesized that the immune microenvironment of the bone marrow influences the progression of myeloma outgrowth in the 5TGM1 transfer model of multiple myeloma. Therefore we sorted bone marrow T, B, NK, neutrophils, and monocytes/macrophages from control and tumor-bearing C57Bl/6 and KaLwRij mice.

2023-02-23 | E-MTAB-12616 | biostudies-arrayexpress

The effect of knockout Brd7 on 4T07-TGL cells under in vitro condition

Project description:Metastasis is a major cause of mortality in cancer and is likely influenced by epigenetic and gene regulatory factors. Using an in vivo screen, we demonstrated that several subunits of the polybromo-associated BAF (PBAF) complex, particularly BRD7, were required for breast cancer metastatic dormancy in lung. BRD7 loss induced metastatic outgrowth, along with modifications in epigenomic landscapes and upregulated oncogenic signaling. Breast cancer cells harboring BRD7 loss also reprogrammed the surrounding immune microenvironment, downregulating MHC-1 expression and promoting a pro-metastatic cytokine profile. Flow cytometric and single-cell analyses revealed increased levels of pro-tumorigenic neutrophils, CD8+ exhausted T cells, and CD4+ stress response T cells in lungs harboring BRD7-deficient metastases. Finally, attenuating this immunosuppressive milieu by neutrophil depletion, neutrophil extracellular trap (NET) inhibition, or immune checkpoint therapy abrogated metastatic outgrowth. These findings, for the first time, implicate BRD7 and PBAF in metastasis, pointing to targetable underlying mechanisms involving specific immune cell compartments.

2024-12-06 | GSE262165 | GEO

the effect of knockout Brd7 on 4T07-TGL cells under in vitro condition [scRNA-Seq]

2024-12-06 | GSE261385 | GEO

the effect of knockout Brd7 on 4T07-TGL cells under in vitro condition

2024-12-06 | GSE260497 | GEO

The effect of knockout Brd7 on 4T07-TGL cells under in vitro condition [RNA-seq]

2024-12-06 | GSE267197 | GEO

Transcriptomic and nuclear architecture of immune cells after LPS-activation

Project description:Changes in the nuclear positioning of specific genes, depending on their expression status, have been observed in a large diversity of physiological processes. However, gene position is poorly documented in immune cells subjected to activation upon bacterial infection. Using the pig as a model organism, we focused our study on monocytes-derived macrophages and neutrophils, the first lines of defense against pathogens. We examine whether changes in gene expression due to LPS-activation imply genes repositioning in the nuclear space. A transcriptomic analysis was first performed to identify the genes differentially expressed and analyse the networks implicated during LPS-IFNγ activation in monocytes-derived macrophages. This allowed us to select 4 up-regulated (IL1β, IL8, CXCL10 and TNFα) and 4 down-regulated (VIM, LGALS3, TUBA3, and IGF2) genes to be further studied by 3D-FISH for their behavior in the nuclear space, particularly towards their chromosome territories (CT) during macrophages activation. Among the 4 up-regulated genes, 3 changed their position during the activation process while the 4 down-regulated ones did not. The analysis of gene behaviors towards their CT was extended to neutrophils for 3 up- and 2 down-regulated genes and similar results were obtained. Our data suggest that relocation in the nuclear space of genes differentially expressed in activated immune cells is gene specific and concern mostly up-regulated ones. Porcine monocyte-derived macrophages: Control vs. LPS-IFNγ activated vs. T-2 toxin/LPS-IFNγ activated. A common reference hybridization scheme was used to compare the three-condition experiment, CM vs. AM vs. TAM. The reference consisted of a pool of RNA from all samples. Biological replicates: 5 control, 5 LPS-IFNγ activated, 5 T-2 toxin/LPS-IFNγ activated independently. One replicate per array.

2011-11-02 | E-GEOD-25491 | biostudies-arrayexpress

MLL3 Loss Drives Metastasis by Promoting a Hybrid Epithelial-Mesenchymal Transition State [ATAC-seq]

Project description:Phenotypic plasticity associated with the hybrid epithelial-mesenchymal transition (EMT) state is crucial to metastatic seeding and outgrowth. We showed that deletion of the epigenetic regulator MLL3, a tumor suppressor frequently altered in human cancer, promoted the acquisition of the hybrid EMT state in both epithelial and mesenchymal breast cancer cells by facilitating EMT and MET, distinct from other known EMT regulators mediating unidirectional changes. MLL3 deletion greatly increased metastasis by enhancing metastatic outgrowth during colonization. Mechanistically, MLL3 loss led to IFNγ signaling upregulation, which contributes to the induction of hybrid EMT cells and the enhanced metastatic capacity.

2022-10-07 | GSE206658 | GEO

MLL3 Loss Drives Metastasis by Promoting a Hybrid Epithelial-Mesenchymal Transition State [ChIP-seq histone marker]

Project description:Phenotypic plasticity associated with the hybrid epithelial-mesenchymal transition (EMT) state is crucial to metastatic seeding and outgrowth. However, the mechanisms controlling the induction of hybrid EMT remain poorly defined. We showed that deletion of the epigenetic regulator MLL3, a tumor suppressor frequently altered in human cancer, promoted the acquisition of the hybrid EMT state in both epithelial and mesenchymal breast cancer cells by facilitating EMT and MET, distinct from other known EMT regulators mediating unidirectional changes. Consequently, MLL3 deletion greatly increased metastasis by enhancing metastatic outgrowth during colonization. Mechanistically, MLL3 loss led to IFNγ signaling upregulation, which contributes to the induction of hybrid EMT cells and the enhanced metastatic capacity.

2022-10-07 | GSE206656 | GEO

MLL3 Loss Drives Metastasis by Promoting a Hybrid Epithelial-Mesenchymal Transition State [ChIP-seq UTX and MLL4]

2022-10-07 | GSE206657 | GEO

Activation of a collaborative innate-adaptive immune response suppresses metastatic breast and ovarian cancer in mice

Project description:Many cancers recruit monocytes/macrophages and polarize them into tumor-associated macrophages (TAMs). TAMs promote tumor growth and metastasis and inhibit cytotoxic T cells, preventing immune control of the cancer. However, macrophages polarized by lipopolysaccharide (a bacteria-derived toll-like receptor 4 [TLR4] agonist) and interferon gamma (IFNγ) instead kill cancer cells. They do so via nitric oxide (NO), generated by inducible NO synthase (iNOS). Altering the polarization of macrophages might therefore be a strategy for controlling tumors. Here, we show that monophosphoryl lipid A (MPLA, a TLR4 agonist used as a vaccine adjuvant)- and IFNγ-activated human macrophages from metastatic breast cancers to kill the same patients’ cancer cells in vitro. Excitingly, intratumoral injection of MPLA with IFNγ not only controlled local tumor growth but also led to reduced metastasis in mouse models of metastatic luminal and triple negative breast cancers. Furthermore, intraperitoneal administration of MPLA and IFNγ reprogrammed peritoneal macrophages and suppressed metastasis in ID8-p53-/- ovarian tumor-bearing mice. We found that the combination of MPLA and IFNγ reprogrammed the immunosuppressive microenvironment to be immunostimulatory by recruiting leukocytes, stimulating type I interferon signaling, reprogramming tumor-associated (CD206+) macrophages to tumoricidal (iNOS+) macrophages, and activating cytotoxic T cells through macrophage-secreted IL12 and TNFα. Both macrophages and T cells, including memory T cells (CD44+CD62L-), were critical for the anti-metastatic effects of MPLA and IFNγ. MPLA and IFNγ are used individually in humans, so our strategy to engage the anti-tumor immune response, which requires no knowledge of unique tumor antigens, may be ready for near-future clinical testing.

2020-09-01 | GSE146211 | GEO

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