The oral–lung axis in lung cancer: microbial translocation, immune reprogramming, and clinical implications

Abstract

The oral–lung axis describes microbial and inflammatory exchange between the oral cavity and the lower respiratory tract. Its relevance to lung cancer is supported by the detection of oral-associated taxa in lower-airway samples, epidemiological links between periodontal disease and lung cancer risk, and experimental evidence that microbial signals can modify epithelial proliferation and antitumor immunity. This review integrates epidemiological, ecological, mechanistic, and translational evidence while distinguishing oral-associated or source-linked observations from pulmonary and intratumoral mechanisms in which oral origin has not been demonstrated. Particular attention is given to repeated microaspiration, Th17/IL-17 inflammation, NOD2/NF-κB and PI3K/ERK signaling, microbial metabolites, and remodeling of the tumor immune microenvironment. Recent studies of pulmonary nodules, radiotherapy, and immune checkpoint inhibition extend this field from disease association to clinically testable questions. The available evidence is most consistent with context-dependent tumor promotion and treatment-response modulation, rather than independent microbial initiation of human lung cancer. We conclude by defining the source-tracking, analytical, prospective, and interventional studies needed to establish causality and clinical utility.