Microbes in the lungs could influence the progression and prognosis of lung cancer

Reviewed by Emily Henderson, B.Sc.November 11, 2020

CONCLUSION: Lung enrichment with oral commensal microbes was associated with advanced disease, poorer prognosis, and tumor progression in lung cancer patients.

Journal in which the study was published: Discovery of cancer, a journal of the American Association for Cancer Research

Author: Leopoldo Segal, MD, director of the Lung Microbiome Program, associate professor of medicine at New York University Grossman School of Medicine and member of NYU Langone’s Perlmutter Cancer Center

Background: “The lungs have long been thought to be sterile, but we now know that oral diners – microbes normally found in the mouth – frequently enter the lungs due to unconscious aspirations,” Segal said. While many studies have shown the impact of the gut microbiome on cancer, the impact of the lung cancer microbiome remains unclear.

Previous research by Segal and colleagues showed that the presence of microbes in the lung can activate the immune response, leading to the recruitment of immune cells and inflammatory proteins such as the cytokine IL-17, which has been shown to modulate the pathogenesis of lung cancer. .

Given the known impact of IL-17 and inflammation on lung cancer, we were interested in determining whether enrichment of oral commensals in the lungs could drive IL-17 inflammation and influence cancer progression and prognosis. of the lung “.

Leopoldo Segal, MD, Director of the Lung Microbiome Program and Associate Professor of Medicine, New York University Grossman School of Medicine

How the study was conducted and results: In this study, Segal and colleagues analyzed the lung microbiomes of 83 untreated adult lung cancer patients using samples obtained from clinical diagnostic bronchoscopy. The samples were analyzed to identify the microbial composition and to determine which genes were expressed in the lung tissue.

The researchers found that patients who had advanced lung cancer (stages 3b-4) had greater enrichment of oral commensals in the lung than those who had early stage disease (stages 1-3a). Furthermore, enrichment of oral commensals in the lung was associated with decreased survival, even after adjustment for tumor stage.

The poor prognosis was associated with the enrichment of the bacteria Veillonella, Prevotella and Streptococcus in the lung microbiome and tumor progression was associated with the enrichment of the bacteria Veillonella, Prevotella, Streptococcus and Rothia.

In patients with early stage disease, enrichment of Veillonella, Prevotella and Streptococcus has been associated with activation of the p53, PI3K / PTEN, ERK and IL-6 / IL-8 signaling pathways.

A strain of Veillonella, found enriched in patients with advanced lung cancer, has been associated with the expression of IL-17, cell adhesion molecules, cytokines and growth factors, as well as with the activation of TNF, PI3K-AKT and pathways JAK-STAT signaling.

Segal and colleagues also looked at the effects of the lung microbiome in a mouse model of lung cancer. They sowed Veillonella parvula into the lungs of mice with lung cancer to model the enrichment of oral diners.

This has led to decreased survival, weight loss and increased tumor burden and has been associated with increased expression of IL-17 and other inflammatory proteins, increased immunosuppressive cell recruitment, and increased immunosuppressive cell recruitment. greater activation of the inflammatory pathways.

To understand the role of IL-17 in lung cancer pathogenesis, Segal and colleagues treated mice enriched with Veillonella parvula with an antibody targeted to IL-17, which resulted in a significant decrease in tumor burden compared to mice treated with a control.

Author comments: “Given the results of our study, it is possible that changes in the lung microbiome could be used as a biomarker to predict prognosis or to stratify patients for treatment,” Segal said. “Another interesting possibility is to target the microbiome itself or the host response to the microbes as a form of cancer therapy. Our results using an antibody against IL-17 suggest that this could be an effective strategy.”

Limitations of the study: A limitation of the study was that the sample size prevented further stratification of patients into subgroups based on the treatments received. Furthermore, since the lung microbiome was only sampled prior to treatment, it was not possible to evaluate changes resulting from the treatment.