Role of the Microbiota in Primary Lung Cancer Initiation and Progression

Abstract Lung cancer is the leading cause of cancer-related death in men in 87 countries and in women in 26 countries. The commensal microbiota lives on the epithelial barriers of the host and is vital for the health of the organism. Specific microbial species have been described to affect neoplastic pathology both at the gastrointestinal tract level and systematically in organs that are not normally associated with the gut microbiota. Studies have revealed the importance of the gut microbiota in the efficacy of anti-cancer therapies (chemo and immunotherapy) However, the role of lung microbiome in lung cancer remains largely unknown. We aimed to study the role of the lung microbiota during lung carcinogenesis progression in the context of p53/K-ras mutation and its impact on the tumor microenvironment. To further analyze the impact of the lung microbiota on lung cancer initiation, P53-Kras mutant germ-free mice will be colonized by intranasal instillation with bacteria identified in human lungs samples from lung cancer patients such as Variovorax paradoxus (V.paradoxus) and Acidovorax temperans (A.temperans) and the tumor burden will be calculated. Our data indicates Germ-free mice instilled with V. paradoxus trended towards an increase tumor burden compared to respective controls while A. temperans -associated germ-free mice seems to delay tumor growth. Germ-free mice, at 18 and 24 weeks post-Ad-Cre virus instillation, tends to have an increased tumor burden than their SPF counterparts. Also, changes in immune infiltrate were observed after flow cytometric analysis with preliminary data showing a decrease in CD45 positives cells the cells in mice instilled with V. paradoxus as well as an increase in Monocytes and Macrophages populations.