Harnessing the immune system in lung cancer: emerging role of the microbiome

The microbiome has emerged as a critical regulator of tumor biology and immune response in lung cancer. Once considered sterile, the lung is now recognized to harbor a diverse microbiome that interacts with the gut-lung axis to shape inflammation, immune evasion, and therapeutic outcomes.

This study reviews current evidence linking microbiome composition and function to lung cancer development and response to immune checkpoint inhibitors (ICIs). We explore mechanisms of microbial influence on host immunity, identify key taxa associated with treatment outcomes, and summarize therapeutic strategies such as fecal microbiota transplantation, probiotics, postbiotics, dietary changes, antibiotics, and engineered live biotherapeutics. The literature search was performed across multiple databases and sources, including PubMed, Scopus, Embase, and clinical trial registries, up to August 2025, focusing on both preclinical and clinical studies related to lung cancer, immunotherapy, and microbiome-targeted interventions.

Microbiome research is redefining precision oncology by presenting new biomarkers and therapeutic targets. Although early-phase trials show potential to improve ICI efficacy, implementation is limited by donor variability, methodological differences, and biosafety issues. Standardized protocols, mechanistic studies, and biomarker-driven patient selection will be crucial to incorporating microbiome modulation into routine lung cancer treatment.