Harnessing the microbiome: a new frontier in lung cancer immunotherapy

Lung cancer is a fatal and the most common malignancy globally. Despite the significant therapeutic benefits of immune checkpoint inhibitors (ICIs), 60%–80% of patients respond poorly to immunotherapy. The identification of reliable predictive biomarkers is essential for implementing precision medicine strategies. In recent years the microbiome has emerged as a promising predictor of immunotherapy outcomes. The influence of the microbiome on lung cancer immunotherapy was systematically and comprehensively reviewed. Moreover, the distinctive microbiome profiles among patients with lung cancer and the correlation with treatment effectiveness are discussed. We investigated the core mechanisms of the interactions between the microbiome and the tumor microenvironment, assessed the usefulness of microbial metabolites as predictive biomarkers, and discussed strategies for microbiome-targeted interventions. Furthermore, we evaluated the current limitations in research methodology and highlighted future research directions, offering novel insights, including multi-site integrated biomarker approaches, site-specific intervention strategies, metabolite-based functional biomarkers, and lung cancer-specific microbiome considerations for developing personalized immunotherapy.