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Efferocytosis fuels malignant pleural effusion through TIMP1

ABSTRACT: Efferocytosis fuels malignant pleural effusion through TIMP1

PROVIDER: PRJNA723335 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14288666_1.fastq.gz	Fastqsanger.gz
	SRR14288666_2.fastq.gz	Fastqsanger.gz
	SRR14288667_1.fastq.gz	Fastqsanger.gz
	SRR14288667_2.fastq.gz	Fastqsanger.gz
	SRR14288668_1.fastq.gz	Fastqsanger.gz

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Efferocytosis fuels malignant pleural effusion through TIMP1

Project description: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.

2021-08-24 | GSE172455 | GEO

Microarray expression profiles of circular RNA in malignant pleural effusion

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Quantitative proteomics revealed novel protein biomarkers to distinguish malignant pleural effusion from benign pleural effusion

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Project description:Pleural effusion (PE) occurs as a consequence of various pathologies. Malignant effusion due to lung cancer is one of the most frequent causes. Methods for accurate differentiation of malignant from benign PE cases are an unmet clinical need. Proteomics profiling of PE has shown promising results. However, mass spectrometry (MS) analysis typically involves the tedious elimination of abundant proteins before analysis, and clinical annotation of proteomics profiled cohorts is limited. In this study, PE from 97 patients was investigated by applying label-free state-of-the-art liquid chromatography-mass spectrometry (LC-MS) to find potential novel biomarkers that correlate with immunohistochemistry assessment of tumor biopsy or survival data. The data set consists of 214 LC-MS runs.

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Pleural effusion

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The RNA Sequencing of B Cells in malignant pleural effusion

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CircRNA_051778 in Exosomes as A Potential Biomarker for Distinguishing Lung Adenocarcinoma-Associated Malignant Pleural Effusion from Tuberculous Pleural Effusion

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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.

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