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Bottom Line: Enrichment of the lungs with oral commensal microbes has been correlated with advanced stage disease, worse prognosis, and tumor progression in patients with lung cancer.
Journal in Which the research was Published: Cancer Discovery, a journal of the American Association for Cancer Research
Author: Leopoldo Segal, MD, director of the Lung Microbiome Program, associate professor of medicine at the New York University Grossman School of Medicine, and member of NYU Langone’s Perlmutter Cancer Center
Wallpaper:”The lungs were thought to be sterile, but we now know that oral commensals–germs normally found at the mouth–frequently enter the lungs due to unconscious aspirations,” said Segal. While many studies have demonstrated the impact of the gut microbiome on cancer, the impact of the lung cancer microbiome remains unclear.
Prior research from Segal and colleagues showed that the presence of germs in the lung may trigger the immune reaction, leading to the recruitment of immune cells and inflammatory proteins like the cytokine IL-17, which was shown to modulate lung cancer pathogenesis.
How the Study was Conducted and Results: In this research, Segal and colleagues examined the lung microbiomes of 83 untreated adult patients with lung cancer using samples obtained from diagnostic clinical bronchoscopies. Samples were analyzed to determine microbial composition and to determine which genes were expressed in lung tissue.
The researchers found that patients who had advanced-stage lung cancer (stages 3b-4) had higher enrichment of oral commensals in the lung compared to those who had early-stage disease (stages 1-3a). Furthermore, the enrichment of oral commensals in the lung was correlated with decreased survival, even after adjusting for tumor phase.
Poor prognosis was connected to the enrichment of Veillonella, Prevotella, and Streptococcus bacteria in the lung microbiome, and tumor development was associated with the enrichment of Veillonella, Prevotella, Streptococcus, and Rothia germs.
In individuals with early-stage disease, enrichment of Veillonella, Prevotella, and Streptococcus was associated with activation of the p53, PI3K/PTEN, ERK, and IL-6/IL-8 signaling pathways.
Given the known impact of IL-17 and inflammation on lung cancer, we were interested in determining if the enrichment of oral commensals in the lungs could drive an IL-17-type inflammation and influence lung cancer progression and prognosis.”
Leopoldo Segal, MD, Director of the Lung Microbiome Program and Associate Professor of Medicine, New York University Grossman School of Medicine
A Veillonella strain, found to be enriched in patients using advanced-stage lung cancer, has been connected to the expression of IL-17, cell adhesion molecules, cytokines, and growth factors, as well as with the activation of the TNF, PI3K-AKT, along with JAK-STAT signaling pathways.
Segal and colleagues examined the impacts of the lung microbiome at a mouse model of lung cancer. They seeded Veillonella parvula in the lungs of mice with lung cancer to model the enrichment of oral commensals.
This led to decreased survival, weight reduction, and increased tumor burden and was correlated with enhanced expression of IL-17 and other inflammatory proteins, higher recruitment of immune-suppressing cells, and enhanced activation of inflammatory pathways.
To understand the use of IL-17 in lung cancer pathogenesis, Segal and colleagues treated Veillonella parvula-enriched mice with an antibody targeted at IL-17, which resulted in a significant decrease in tumor burden compared to mice treated with a controller.
Author’s Comments:”Given the results of our analysis, it is likely that changes to the lung microbiome can be utilized as a biomarker to predict prognosis or to stratify patients for treatment,” said Segal. “Another intriguing possibility is to target the microbiome itself or the host response to germs as a kind of cancer treatment. Our results using an antibody against IL-17 suggest that this might be an effective strategy.”
Study Limitations: A limitation of this analysis was that the sample size avoided further stratification of patients into subgroups based on the treatments they received. Additionally, since the lung microbiome was just sampled before treatment, changes caused by treatment could not be assessed.
American Association for Cancer Research