Abstract

Lung cancer development is associated with local commensal microbiota dysbiosis and inflammation. Currently, reports demonstrated that a diverse commensal microbiota colonizes the lung, and the lower respiratory tract infections commonly present in lung adenocarcinoma patients are linked to clinical outcomes. At present, there are limited research on how local commensal microbiota affects the process of lung adenocarcinoma. In this study, we prove that depletion of commensal microbiota suppresses lung adenocarcinoma progression. Mice administered lung commensal microbiota before injected lung cancer cells had a lower tumor burden than no antibiotic-treated mice. Notably, single-cell RNA sequencing revealed that the distribution of Spp1+ macrophage was reduced after lung commensal microbiota destruction. Here, specific cell population interacted with neutrophil namely SPP1-CD44 was identified, which was the dominant contributor to tumor progression. Moreover, the Spp1+ macrophage increased in late stage patients and was associated with poor prognosis. Overall, our finding demonstrated that local airway microbiota modulates the host immune tone in lung adenocarcinoma by affecting Spp1+ macrophages and thereby defining key cell subsets and cytokines that may serve as effective adjunct targets in immunotherapy of lung cancer.