Pulmonary microbiota is a hidden link between lung cancer Development and microenvironment: Potential for future immune therapeutic strategies.

Lung, as a vital interface with the external environment, hosts a diverse microbiota that plays a significant role in lung cancer development. The dual role of pulmonary microbiota is characterized by its potential to trigger chronic inflammation(precursor of cancer), and its ability to stimulate anti-tumor immune responses. In lung cancer patients, the pulmonary microbiota often exhibits reduced bacterial diversity and over representation of pathogenic bacteria. Distinct pathological types of lung cancer, and clinical stage of lung cancer were correlates with variations in microbial diversity. Particular focus on its influence on the immune microenvironment have also been delved. Including immune cells, inflammatory signaling pathways, microbiota-metabolic interactions, and modulation of the programmed cell death protein 1(PD-1)/ programmed death-ligand 1 (PD-L1) checkpoint, which is crucial for tumor immune evasion. Understanding these interactions is essential for optimizing lung cancer immunotherapy strategies. For instance, antibiotics may reduce the efficacy of immune checkpoint inhibitors (ICIs), especially in lung cancer patients with high PD-L1 expression or EGFR-mutant NSCLC. Additionally, new therapeutic interventions, such as microbiome-targeted therapies or probiotics, are suggested to enhance the efficacy of ICIs. By uniquely integrating clinical correlations with mechanistic insights on immune microenvironment, this may render pulmonary microbiota to be potential therapeutic strategies for future immunotherapy treatments.