Lower respiratory microbiota as modulators of tumor immunity in lung adenocarcinoma

BACKGROUND: Lung adenocarcinoma is common type of cancer with high morbidity and mortality. Emerging evidence suggests that microbial colonization in the lower respiratory airways may modulate immune activation and response to immunotherapy. However, the immunologic relevance of microbiome diversity in lung cancer remains unclear. METHODS: We analyzed bronchoalveolar lavage fluid (BALF), serum cytokines, immune cell subsets, and checkpoint molecule expression from 350 patients with lung adenocarcinoma. Microbiome diversity was quantified by phylum- and genus-level richness derived from binary detection of specific bacterial groups. Associations between microbial diversity, immune parameters, and clinical prognosis were evaluated using correlation and comparative statistical analyses. RESULTS: Among 350 samples, there was no major compositional difference between patients who died and those who recovered. Microbial diversity showed no significant associations with systemic cytokines, including IL-6, IL-1β, TNF-α, IL-10, and IFN-γ. Genus richness showed positive correlation with PD-1 expression, while phylum richness correlated inversely with PD-L1. Specific taxa demonstrated distinct immune associations: TM7 correlated with increased regulatory T cells, Actinobacteria and Veillonella correlated with lower IL-1β, while Neisseria correlated with CTLA-4 expression. CONCLUSION: Lower airway microbiota in lung adenocarcinoma display moderate diversity and meaningful immunologic associations, particularly with PD-1/PD-L1 pathways, Tregs, and IL-1β regulation. Although diversity alone is not prognostic, specific microbial taxa may shape immune landscapes relevant to immunotherapy response and represent potential targets for future microbiome-based interventions. CLINICAL TRIAL NUMBER: Not applicable.