Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Efferocytosis fuels malignant pleural effusion through TIMP1

ABSTRACT: Malignant Pleural Effusion (MPE) results from the capacity of several human cancers to metastasize to the pleural cavity. The median survival is 3-12 months and no effective treatments are currently available. Immune-based therapies have failed until now, reflecting our insufficient understanding of the basic immunological mechanisms leading to MPE progression. Here, we show that phagocytosis of apoptotic cells in the pleural cavity fuels the progression of MPE. We found that efferocytosis through the receptor tyrosine kinases AXL and MERTK in macrophages led to the production of IL-10. Using single cell RNA-Seq, we revealed that IL-10 is indeed produced by four distinct pleural cavity macrophage subpopulations characterized by different metabolic states and cell chemotaxis properties. In turn, IL-10 acts on dendritic cells (DCs) inducing the production of tissue inhibitor of metalloproteinases 1 (TIMP1). Genetic ablation of AXL and MERTK in macrophages or IL-10 receptor in DCs or TIMP1 significantly reduced MPE progression. Taken together, our results delineate an inflammatory cascade – from the clearance of apoptotic cells by macrophages, to production of IL-10, to induction of TIMP1 in DCs – that facilitates MPE progression. This inflammatory cascade offers a series of targets for therapies which aim at preventing or treating MPE.

ORGANISM(S): Mus musculus

PROVIDER: GSE172455 | GEO | 2021/08/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

mRNA expression data from macrophages in malignant pleural effusion of wild type and IL-10 deficency mice

Project description:Malignant pleural effusion (MPE) is a common medical problem caused by multiple malignancies especially lung cancers and always along with a poor therapeutic outcome.Interlukin-10 (IL-10) promotes the formation and development of malignant pleural effusion (MPE). In the current study, our results showed that IL-10 deficiency decreased the percentage of macrophages in mice MPE and regulated M1/M2 polarization in vivo and vitro. The migration capacity of tumor cells was suppressed, and apoptosis was promoted when co-cultured with MPE macrophages in the absence of IL-10.

2023-08-09 | GSE220281 | GEO

Intrapleural nano-immunotherapy promotes innate and adaptive immune responses to enhance anti-PD-L1 therapy for malignant pleural effusion

Project description:Malignant pleural effusion (MPE) is indicative of terminal malignancy with uniformly fatal prognosis. Often, two distinct compartments of tumor microenvironment, the effusion and disseminated pleural tumors, co-exist in the pleural cavity, presenting a major challenge for therapeutic interventions and drug delivery. Clinical evidence suggests that MPE comprises abundant tumor associated myeloid cells with the tumor-promoting phenotype, impairing antitumor immunity. Here, we developed liposomal cyclic dinucleotide (LNP-CDN) for targeted activation of STING signaling in macrophages and dendritic cells and showed that, upon intrapleural administration, they induce drastic changes in the transcriptional landscape in MPE, mitigating the immune cold MPE in both the effusion and pleural tumors. Moreover, combination immunotherapy with blockade of PD-L1 potently reduced MPE volume and inhibited tumor growth not only in pleural cavity but also in lung parenchyma, conferring significantly prolonged survival of MPE-bearing mice. Furthermore, the LNP-CDN-induced immunological effects were also observed with clinical MPE samples, suggesting the potential of intrapleural LNP-CDN for clinical MPE immunotherapy.

2021-09-21 | GSE164487 | GEO

Intrapleural nano-immunotherapy promotes innate and adaptive immune responses to enhance anti-PD-L1 therapy for malignant pleural effusion

2021-09-21 | GSE179783 | GEO

microRNA expression data from nucleated cells excluding tumor cells in malignant pleural effusion (MPE) from WT and IL-10 knock out (IL-10-/-)

Project description:The interactions between tumor cells and the host vasculature and immune cells results in increased net fluid production via enhanced plasma extravasation into the pleural space.Understanding the regulatory mechanism of IL-10 in MPE formation is essential both for deciphering how IL-10 acts in regulating tumor immunity and for discovering key molecular targets for intervention in advanced cancers. We investigate the characteristic of microRNAs (miRNAs) in IL-10 induced murine MPE. Identifing the distinct classes of up-regulated and down-regulated miRNAs during this process.

2019-08-19 | GSE135939 | GEO

mRNA expression in CD4+ T cells of malignant pleural effusion (MPE) from WT and IL-10 knock out mice

2019-08-27 | GSE136345 | GEO

Survival and pleurodesis response markers in malignant pleural effusion – The PROMISE study

Project description:Background: Malignant pleural effusion (MPE) is a common condition that indicates advanced malignancy, incurability and short life expectancy. While MPE incidence is increasing worldwide, prognostic biomarkers to plan treatment and to understand the underlying mechanisms of disease progression remain unidentified. Objective: To discover, validate, and prospectively assess biomarkers of survival and pleurodesis response in MPE. To combine clinical, radiologic, and pleural fluid biologic parameters in order to build a score that forecasts survival. Conclusions: The PROMISE score is the first prospectively validated prognostic model for MPE that combines biological and clinical parameters to accurately estimate 3-month mortality.

2018-07-17 | PXD008682 | Pride

CCL11/CCR3-dependent eosinophilia alleviates malignant pleural effusions and improves prognosis

Project description:The role of eosinophils in the development and progression of malignant pleural effusion (MPE) remains unclear. However, MPE is a frequently occurring manifestation of advanced cancer and is often associated with a poor prognosis. While current treatment options for MPE can provide palliative care, alternative therapies are urgently needed. To investigate this role, eosinophil counts were determined using flow cytometry and immunofluorescence. Eosinophil-deficient mice (Eos-null) and Cd3δ -promoter Il5 transgenic (Il5 Tg) mice were subjected to a mouse model of MPE. Eosinophils were isolated by magnetic-activated cell sorting (MACS) and fluorescence-activated cell sorting (FACS), and their transcriptional profile was obtained by RNA sequencing. Finally, we evaluated the effects of the C-C motif chemokine ligand 11 (CCL11) and a C-C motif chemokine receptor 3 (CCR3) axis on MPE pathology using recombinant mouse CCL11 and a CCR3 inhibitor. In humans, eosinophil counts were increased in MPE and negatively correlated with the LENT score. In animal models, eosinophils were rapidly recruited to the pleural cavity when challenged with tumor cells. Interestingly, eosinophil deficiency worsened MPE, while an increase in eosinophils through various methods improved MPE. Furthermore, the recruitment of eosinophils may be influenced by the CCL11-CCR3 axis. Taken together, the study highlights the protective role of eosinophils against MPE formation, indicating their potential as a therapeutic strategy. Moreover, the CCL11-CCR3 axis may be a viable target for MPE treatment.

2024-08-01 | GSE245575 | GEO

The cellular landscape of breast cancer associated malignant pleural effusions

Project description:Malignant pleural effusions (MPE) are a common complication of advanced cancers, particularly those adjacent to the pleura such as lung and breast cancer and are a frequent complication in metastatic disease. The pathophysiology of MPE formation in advanced breast cancer remains poorly understood, and their composition and biology are understudied. To characterise the phenotypic diversity of malignant pleural effusion, we performed single-cell RNA sequencing on 10 MPEs from 7 metastatic breast cancer patients with diverse molecular subtypes: two triple negative (TNBC) patients, three luminal B patients including one with a rare inflammatory subtype, and two luminal A patients. For all patients, we sequenced cells from the entire MPE, without performing any enrichment or selection, in order to ascertain the cellular composition and molecular phenotypes in an unbiased manner. Our dataset presents the first unbiased and unselected assessment of breast cancer associated MPEs at single cell resolution, providing the community with a vital resource for the study of MPEs. Our work highlights the molecular and cellular diversity captured in MPEs and advances the use of these clinically relevant biopsies both in monitoring disease progression and in the development of targeted therapeutics for patients with advanced breast cancer.

2022-11-30 | GSE208532 | GEO

Mertk negatively regulates adaptive immunity

Project description:Tolerogenic dendritic cells (tol-DCs) offer a promising therapeutic potential for autoimmune diseases. Tol-DCs have been reported to inhibit immunogenic responses, yet little is known about the mechanisms controlling their tolerogenic status, as well as associated specific markers. Here we show that the anti-inflammatory TAM receptor tyrosine kinase MERTK, is highly expressed on clinical grade dexamethasone-induced human tol-DCs and mediates their tolerogenic effect. Neutralization of MERTK in allogenic mixed lymphocyte reactions as well as autologous DC-T cell cultures leads to increased T cell proliferation and IFN-g production. Additionally, we identify a previously unrecognized non-cell autonomous regulatory function of MERTK expressed on DCs. Recombinant Mer-Fc protein, used to mimic MERTK on DCs, suppresses naïve and antigen-specific memory T cell activation. This mechanism is mediated by the neutralization of the MERTK agonist Protein S (PROS1) expressed by T cells. We find that MERTK and PROS1 are expressed in human T cells upon TCR activation and drive an autocrine pro-proliferative mechanism. Collectively, these results suggest that MERTK on tol-DCs directly inhibits T cell activation through the competition for PROS1 interaction with MERTK in the T cells. Targeting MERTK may provide an interesting approach to effectively increase or suppress tolerance for the purpose of immunotherapy. The complete database comprised the expression measurements of 54,675 genes for: immature (n=9), mature (n=7) and tolerogenic (n=8). Influence of treatment with dexamethasone (n=3) and LPS (n=2) are included.

2015-01-29 | E-GEOD-56017 | biostudies-arrayexpress

Microarray expression profiles of circular RNA in malignant pleural effusion

Project description:To explore the expression pattern of circular RNAs (circRNAs) and their biological functions in malignant pleural effusion, we surveyed the circRNA expression profiles of 3 lung adenocarcinoma-associated malignant pleural effusion (LA-MPE) and 3 tuberculous pleural effusion (TPE) from clinical patients using Clariom D human microarray.

2023-05-01 | GSE122427 | 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