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Bronchoalveolar lavage fluid reveals factors contributing to the efficacy of PD-1 blockade in lung cancer

ABSTRACT: Bronchoalveolar lavage is commonly performed to examine inflammation and responsible pathogens in lung diseases, and its findings may be used to assess the immune profile of the lung tumor microenvironment (TME). To investigate whether analyses of bronchoalveolar lavage fluid (BALF) can help identify non-small cell lung cancer (NSCLC) patients who respond to immune checkpoint inhibitors (ICIs), BALF and blood were prospectively collected before initiating nivolumab. The secreted molecules, microbiome, and cellular profiles based on BALF and blood analysis were compared regarding therapeutic effect in 12 patients. Compared to non-responders, responders showed significantly higher CXCL9 levels and greater diversity in the lung microbiome profile in BALF, and greater frequency of CD56+ subset in blood T cells, whereas no significant difference was found in PD-L1 expression of tumor cells. Antibiotic treatment in a preclinical lung cancer model significantly decreased CXCL9 in the lung TME, resulting in reduced sensitivity to nivolumab, which was reversed by CXCL9 induction in tumor cells. Thus, CXCL9 and the microbiome in the lung TME might be associated with each other, and their balance could contribute to nivolumab sensitivity in NSCLC patients. BALF analysis can help predict the efficacy of ICIs when performed along with currently approved examinations.

ORGANISM(S): Homo sapiens

PROVIDER: GSE193049 | GEO | 2022/04/07

REPOSITORIES: GEO

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Azithromycin effects on lung microbiome in COPD patient

Project description:Azithromycin (AZM) reduces pulmonary inflammation and exacerbations in chronic obstructive pulmonary disease patients with emphysema. The antimicrobial effects of AZM on the lung microbiome are not known and may contribute to its beneficial effects. Methods. Twenty smokers with emphysema were randomized to receive AZM 250 mg or placebo daily for 8 weeks. Bronchoalveolar lavage (BAL) was performed at baseline and after treatment. Measurements included: rDNA gene quantity and sequence. Results. Compared with placebo, AZM did not alter bacterial burden but reduced Î±-diversity, decreasing 11 low abundance taxa, none of which are classical pulmonary pathogens. Conclusions. AZM treatment the lung microbiome Randomized trial comparing azithromycin (AZM) treatment with placebo for eight weeks. Bronchoalveolar lavage (BAL) samples were obtained before and after treatment to explore the effects of AZM on microbiome, in the lower airways. 16S rRNA was quantified and sequenced (MiSeq) The amplicons from total 39 samples are barcoded and the barcode is provided in the metadata_complete.txt file.

2016-07-19 | E-GEOD-74396 | biostudies-arrayexpress

small RNA expression in lung extracellular vesicles (EV) from C57BL/6J mice exposed to ozone

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BALF proteomics - In-depth proteomic analysis of human bronchoalveolar lavage fluid towards the biomarker discovery for lung cancers

Project description:Lung cancer is one of the most common cancers and the leading cause of cancer-related mortality. Because the early diagnosis of the cancer is one of the major goals in lung cancer research, the molecule-based sensitive detection of biomarkers from bronchoalveolar lavage fluid (BALF) to diagnose the lung cancer has been suggested as a promising method. BALF is a fluid that can be easily obtained from patients with lung diseases and the process of collecting the fluid is relatively cheap and non-invasive. Here, we developed a novel method for in-depth single proteomic analysis of BALF by using antibody-based depletion of high abundant proteins from BALF. We identified, in total, 4,615 protein groups mapped to 4,535 gene names using LC-MS/MS. We found our method outperformed conventional methods. With the comprehensive result, we believe that this method would facilitate lung cancer biomarker discovery.

2019-05-30 | PXD012645 | Pride

Gene expression profile at single cell level of Bronchoalveolar Lavage fluid (BALF) cells from mice

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2a8d9e3c-3a68-4472-b4b7-40985237aca5 - samples

Project description:CTD-ILD BALF and blood scRNA-seq dataset consists of single-cell transcriptome data of bronchoalveolar lavage fluid (BALF) and blood derived from 30 connective tissue disease-associated interstitial lung disease (CTD-ILD) and 12 idiopathic interstitial pneumonia (IIP) patients.

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Novel Protein Pathways in Development and Progression of Pulmonary Sarcoidosis.

Project description:Sarcoidosis is a disease that affects multiple organ systems, with lung disease seen commonly and is the most frequent cause of sarcoidosis-related mortality. We investigated to compare protein expression in the lung from both bronchoalveolar lavage fluid (BAL) cells and fluid (BALF) in newly diagnosed patients with sarcoidosis. Mass spectral data acquisition was conducted on an Orbitrap Fusion instrument in data-dependent mode using either label-free (BALF) or label-based (intracellular) approach. We identified 4,306 high confidence intracellular proteins (probability >99%) with 272 differentially expressed proteins controlling for an FDR 5%. The protein map to several known canonical pathways including phagosome maturation, clathrin-mediated endocytic signaling, NRF-2 mediated oxidant stress response, The examination of BALF identified 1,192 proteins, xxx and xxx protein with differential expression between controls vs. sarcoidosis and progressive vs. non-progressive sarcoidosis respectively. Several of the proteins identified mapping to the differentially expressed proteins were also detected in the BALF.

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Quantitative proteomic analysis of bronchoalveolar lavage fluid in West Highland white terriers with canine idiopathic pulmonary fibrosis C4PR_LIV

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2022-05-20 | PXD028916 | Pride

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Project description:Immune characteristics associated with Coronavirus Disease-2019 (COVID-19) severity are currently unclear. We characterized bronchoalveolar lavage fluid (BALF) immune cells from patients with varying severity of COVID-19 disease and from healthy subjects using single-cell RNA-sequencing. Proinflammatory monocyte-derived macrophages were abundant in the BALF from severe COVID-9 patients. Moderate cases were characterized by the presence of highly clonally expanded tissue-resident CD8+ T cells. This atlas of the bronchoalveolar immune-microenvironment suggests potential mechanisms underlying pathogenesis and recovery in COVID-19.

2020-04-22 | GSE145926 | GEO

A Prototypic Small Molecule Database for Bronchoalveolar Lavage-Based Metabolomics

Project description:The analysis of bronchoalveolar lavage fluid (BALF) using mass spectrometry-based metabolomics can provide insight into lung diseases, such as asthma. However, the important step of compound identification is hindered by the lack of a small molecule database that is specific for BALF. Here we describe prototypic, small molecule databases derived from human BALF samples (n=117). Human BALF was extracted into lipid and aqueous fractions and analyzed using liquid chromatography mass spectrometry. Following filtering to reduce contaminants and artifacts, the resulting BALF databases (BALF-DBs) contain 11,737 lipid and 658 aqueous compounds. Over 10% of these were found in 100% of samples. Testing the BALF-DBs using nested test sets produced a 99% match rate for lipids and 47% match rate for aqueous molecules. Searching an independent dataset resulted in 45% matching to the lipid BALF-DB compared to < 25% when general databases are searched. Overall, the BALF-DBs can reduce false positives and improve confidence in compound identification compared to when general databases are used.

2018-02-09 | MTBLS591 | MetaboLights

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