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REVIEW article

Front. Immunol.

Sec. Cancer Immunity and Immunotherapy

This article is part of the Research TopicThe Respiratory System Microbiome: Diversity, Function and HealthView all 11 articles

Respiratory Microbiome-Host Interaction on Lung Carcinogenesis, Immunity, and Immunotherapy

Provisionally accepted
Peng  WangPeng Wang1,2Cuihong  GeCuihong Ge1,2Qijia  HanQijia Han2Xinru  JingXinru Jing2Mingzhu  WangMingzhu Wang3Minghua  HuangMinghua Huang2Zhiming  XiangZhiming Xiang2*
  • 1Postgraduate cultivation base of Guangzhou University of Chinese Medicine, Panyu Central Hospital, Guangzhou, China
  • 2The Affiliated Panyu Central Hospital of Guangzhou Medical University Department of Radiology, Guangzhou, China
  • 3Department of Gynecology, The Affiliated Panyu Central Hospital of Guangzhou Medical University, Guangzhou, China

The final, formatted version of the article will be published soon.

The respiratory microbiome, as an integral component of the lung cancer microenvironment, exerts pivotal influences on tumorigenesis, immune homeostasis, and therapeutic response through intricate crosstalk with host immunity. Despite advancements, current limitations in lung cancer immunotherapy persist, including heterogeneous therapeutic responses, immune-related adverse events, and the lack of predictive biomarkers. These unmet clinical needs underscore the imperative to delineate the complex immune landscape of respiratory microbiome in lung cancer pathogenesis. This review systematically analyzes the hallmarks of respiratory dysbiosis (reduced α-diversity and enrichment of Streptococcus and Veillonella) and their associations with lung cancer staging, histological subtypes, and prognosis. We further elucidate how these microbial alterations influence tumor progression via metabolic-epigenetic-immune pathways. Additionally, we establish clinical correlations between microbiome signatures and both immune checkpoint inhibitor therapeutic efficacy/toxicity profiles, while examining the paradoxical effects of antibiotic exposure during immunotherapy. Emerging intervention strategies targeting the respiratory microbiome, such as aerosolized probiotics, engineered bacteria (e.g., Escherichia coli), and microbiota-derived nanomaterials, showcase potential in remodeling antitumor immunity and improving therapeutic outcomes. Our findings highlight the double-edged sword effect of the respiratory microbiota as biomarkers and therapeutic targets in lung cancer management, providing critical insights for clinical translation.

Keywords: Respiratory microbiome, Non-small cell lung cancer, Immunity, Immunotherapy, antibiotics

Received: 30 Jul 2025; Accepted: 10 Nov 2025.

Copyright: © 2025 Wang, Ge, Han, Jing, Wang, Huang and Xiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Zhiming Xiang, xiangzhiming@pyhospital.com.cn

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