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

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

PROVIDER: PRJNA794829 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17452593.fastq.gz	Fastqsanger.gz
	SRR17452594.fastq.gz	Fastqsanger.gz
	SRR17452595.fastq.gz	Fastqsanger.gz
	SRR17452596.fastq.gz	Fastqsanger.gz
	SRR17452597.fastq.gz	Fastqsanger.gz

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

Project description: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.

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Bronchoalveolar lavage, sputum, background

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

Project description:Bronchoalveolar lavage is commonly performed to assess inflammation and identify responsible pathogens in lung diseases. Findings from bronchoalveolar lavage might be used to evaluate the immune profile of the lung tumor microenvironment (TME). To investigate whether bronchoalveolar lavage fluid (BALF) analysis can help identify patients with non-small cell lung cancer (NSCLC) 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 of 12 patients were compared with regard to therapeutic effect. Compared with ICI nonresponders, responders showed significantly higher CXCL9 levels and a greater diversity of the lung microbiome profile in BALF, along with a greater frequency of the CD56+ subset in blood T cells, whereas no significant difference in PD-L1 expression was found in tumor cells. Antibiotic treatment in a preclinical lung cancer model significantly decreased CXCL9 in the lung TME, resulting in reduced sensitivity to anti-PD-1 antibody, which was reversed by CXCL9 induction in tumor cells. Thus, CXCL9 might be associated with the lung TME microbiome, and the balance of CXCL9 and lung TME microbiome could contribute to nivolumab sensitivity in patients with NSCLC. BALF analysis can help predict the efficacy of ICIs when performed along with currently approved examinations.

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Project description:In dogs, a species for which markers of cell populations are often limiting, we sought to evaluate in an unbiased way the heterogeneity of cell subpopulations in the bronchoalveolar lavage fluid of healthy dogs, by single-cell RNA-sequencing.

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

Project description:Bronchoalveolar Lavage cells include resident and infiltrating immune cells in repsone to infections. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of BALF cells.

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