Abstract
Intratumoral microbiota, once considered passive bystanders, are now recognized as active modulators of the tumor immune microenvironment (TIME)-the complex network of immune cells, stromal components, and signaling molecules within tumors-and ultimately shape immunotherapy outcomes in lung cancer. This review aims to elucidate the exact roles of intratumoral microbiota in lung cancer immuno-therapy responses and the potential mechanism, offering novel perspectives for overcoming resistance. We conducted a narrative review of the literature using a PubMed and Web of Science search of articles written in English from inception to November 2025. We summarize current evidence on the characteristics of intratumoral microbiota in lung cancer and their associations with patient outcomes following immune checkpoint inhibitor (ICI) treatment. We discuss how intratumoral microbes, their metabolites, and extracellular vesicles influence and remodel TIME, thereby either promoting or counteracting ICI efficacy. Furthermore, we explore the potential of microbial signatures as predictive biomarkers and highlight microbiota-targeted strategies-including probiotics, engineered bacteria, and rational antibiotic use-to overcome resistance and enhance clinical benefits. Collectively, available data support intratumoral microbiota as crucial modulators and promising therapeutic targets in lung cancer, and decoding their multifaceted interactions may inform precision microbiota-targeting strategies to improve patient outcomes.