The Role of Lung Microbiome in Lung Cancer: From Mechanisms to Clinical Implications

Lung cancer is the most common cancer type and the most common cause of cancer-related deaths worldwide. Recently, the lung microbiome has garnered significant attention as a novel therapeutic target for lung cancer. Next-generation sequencing technologies have revealed the existence of a lung microbiome, suggesting a close association between lung microorganisms and the development of lung cancer. This interaction is mediated through various pathways, including immune modulation, alteration of cellular niches and drug metabolism, which ultimately affects lung cancer progression. This review synthesizes pioneering advances from the past 2 decades that redefine the lung microbiome as a functional mediator, rather than a passive marker, of lung cancer pathogenesis, with mechanistic insights rigorously derived from integrated in vitro and in vivo studies. Through coculture models and animal experiments, key microbial shifts, such as enrichment of Streptococcus and Veillonella and depletion of Neisseria, have been found to contribute to cancer progression via activation of immune pathways (eg, TLR2 and γδ T cells) and sustained proinflammatory signaling. Clinically, microbial biomarkers (eg, Capnocytophaga and human papillomavirus) and microbiota-targeted therapies (eg, nebulized antibiotics and IL-17A blockade) show promise for diagnosis and treatment. These insights underscore the potential of the lung microbiome as a source of biomarkers and therapeutic targets, urging future research to elucidate mechanisms, validate findings in larger cohorts and translate discoveries into personalized strategies for early detection and improved outcomes.