Abstract
BACKGROUND AND OBJECTIVE: Recent studies have increasingly highlighted the critical role of the microbiome in lung cancer initiation, progression, metastasis, and therapeutic resistance. Microbial dysbiosis has been identified as a significant risk factor for lung cancer progression. Beyond the gut, emerging evidence shows that microorganisms also colonize the lungs and even inside tumors, suggesting a broader role of the microbiome in the disease. This review explores the immune-oncology-microbiome (IOM) axis by examining microbial communities across different anatomical sites, their interactions with the tumor immune microenvironment, and their impact on immunotherapy efficacy in lung cancer. METHODS: We conducted a systematic literature search using PubMed and Web of Science databases for English-language articles published between 2014 and 2025, using key terms related to lung cancer and microbiome. KEY CONTENT AND FINDINGS: The microbiome associated with lung cancer encompasses gut microbiota, lower respiratory tract microbiota, and intratumor microbiota. Different microbial communities maintain microecological homeostasis and modulate antitumor immune responses by shaping the tumor immune microenvironment. Meanwhile, certain microbiota can enhance or hinder the effectiveness of immunotherapy. CONCLUSIONS: The IOM axis reveals dynamic interactions between immune cells, cancer cells, and microbes. Specific microbe-derived metabolites show promise as lung cancer biomarkers. Current microbiome-based therapy shows great potential in lung cancer treatment.