The commensal microbiome in respiratory tract tumors: From oncogenic mechanisms to clinical translation

BACKGROUND: The human commensal microbiome, commonly recognized as a "second genome", exerts a crucial regulatory role in host metabolism, immune homeostasis maintenance, and the progression of various diseases. Respiratory tract tumors remain a leading cause of global cancer-related deaths due to their high invasiveness and late-stage diagnosis. With the rapid development of high-throughput sequencing technology, the complex associations between microbial communities and respiratory tract tumors have been gradually uncovered. In lung cancer, distinct microbiota-related signatures, including tissue-specific and microbiota-derived ones have been identified, showing variations across cancer subtypes, anatomical sample sources, and patient demographics. These findings collectively lay the foundation for in-depth investigations into the interplay between the microbiome and respiratory tract tumors. AIM OF REVIEW: This review aims to systematically synthesize the current understanding of the commensal microbiome across respiratory tract tumors, primarily taking lung cancer as the main example, with systematic extensions to other respiratory tract malignancies, including laryngeal carcinoma and nasopharyngeal carcinoma, focusing on clarifying the ecological characteristics of microorganisms, elucidating the mechanistic links between the microbiome and tumorigenesis as well as progression, and summarizing the translational value of the microbiome in clinical practice, including applications in diagnostics, therapeutics, and prognostic evaluation. KEY SCIENTIFIC CONCEPTS OF REVIEW: Emerging evidence highlights that the microbiome contributes to the initiation of respiratory tract tumors through multiple pathways: dysbiosis-induced chronic inflammation, immune system dysregulation, and metabolite-mediated epigenetic or functional alterations. Beyond tumorigenesis, the microbiome also plays a vital role in modulating the efficacy of cancer treatments, particularly conventional therapies and immunotherapies. Additionally, the microbiome provides novel opportunities for the development of diagnostic biomarkers and microbiome-targeted intervention strategies. Its prognostic potential in predicting recurrence, metastasis, and survival is increasingly recognized. These core scientific concepts collectively constitute the theoretical framework for exploring the microbiome's role in respiratory tract tumor research and clinical translation.