Microbial architects of the lung tumor niche: integrating intratumoral and lung cancer-associated microbiome

Abstract

Lung cancer (LC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Increasing evidence suggests that both the lung cancer-associated microbiome and the intratumoral microbiome are important components of the tumor ecosystem and contribute to cancer development, progression, and therapeutic response. Distinct microbial alterations have been identified in the lower airway, bronchoalveolar lavage fluid, airway epithelium, and tumor tissues, indicating complex host-microbe interactions across multiple microbial niches. Mechanistically, these microbial communities may influence tumor biology through microbial metabolites, chronic inflammation, immune modulation, and remodeling of the tumor microenvironment. In addition, specific microbial signatures have been associated with disease diagnosis, prognosis, recurrence, and treatment outcomes, highlighting their potential clinical value. This review integrates current advances in lung cancer-associated and intratumoral microbiota, summarizes their biological and clinical significance, and discusses key methodological challenges and future directions for clinical translation.