A recent paper, published in Cancer Discovery, has found that enrichment of the lungs with oral commensal microbes was associated with advanced stage disease, worse prognosis and tumour progression in lung cancer patients.
Lung cancer
Lung cancer remains the leading cause of cancer death worldwide. In the past year, lung cancer has led to 1.7 million deaths. While targeting specific somatic mutations has improved survival, it has only been effective in ~30% of subjects with lung adenocarcinomas. Immunotherapies that target inhibitor checkpoint molecules (e.g. PD-1) have shown some promise in affecting T cell responses and improving survival. Nonetheless, 40-60% of patients do not respond or develop resistance to immunotherapy.
Recent studies have identified gut microbiota signatures that are associated with augmenting anti-tumour immunity and PD-1 blockade response in murine models. To date, no human studies have explored the lower airway microbiota and lung cancer prognosis. This is surprising considering the growing evidence supporting the role of the lung microbiota in lower airway inflammation.
Lung microbiome
In this study, researchers analysed the lung microbiomes of 83 untreated adult patients with lung cancer. They specifically used samples from diagnostic clinical bronchoscopies. The samples were analysed to identify microbial composition and to determine which genes were expressed in lung tissue.
The team found that patients with advanced-stage lung cancer (stages 3b-4) had greater enrichment of oral commensals in the lung than those who had early-stage disease (stages 1-3a). Additionally, the enrichment of oral commensals in the lung was associated with decreased survival, even after adjusting for tumour stage. Specifically, Veillonella, Prevotella, and Streptococcus bacteria associated with poor prognosis. While, Veillonella, Prevotella, Streptococcus, and Rothia bacteria were associated with tumour progression. In patients with early-stage disease, enrichment of Veillonella, Prevotella, and Streptococcus associated with activation of the p53, PI3K/PTEN, ERK, and IL-6/IL-8 signalling pathways.
Other analyses within murine models of lung cancer found that Veillonella parvula resulted in decreased survival. It also led to increased tumour burden, an IL-17 inflammatory phenotype and activation of checkpoint inhibitor markers.
Conclusion
These results support that local airway microbiota modulate host immune environment in lung cancer, affecting tumour progression and prognosis. A better understanding of this microbial-host interaction in the lower airways is critical. This will help uncover how lung cancer-associated microbiota could be modulated to impact prognosis and response to immunotherapies.
Leopoldo Segal, author and Director of the Lung Microbiome Program and Associate Professor of Medicine at the NYU Grossman School of Medicine, stated:
“Given the results of our study, it is possible that changes to the lung microbiome could be used as a biomarker to predict prognosis or to stratify patients for treatment.
Another exciting possibility is to target the microbiome itself or the host response to microbes as a form of cancer therapy. Our results using an antibody against IL-17 suggest that this could be an effective strategy.”
Image credit: By starline – www.freepik.com
