The Lung Microbiota and Lung Cancer: A Growing Relationship
Abstract
:Simple Summary
Abstract
1. Introduction
2. Lung Microbiota and Non-Cancerous Diseases
3. Lung Microbiota and Lung Cancer Pathogenesis
3.1. Lung Cancer Initiation
3.2. Lung Cancer Progression
4. Microbiota as a Therapeutic Target in Lung Cancer
4.1. Microbiota and Immunotherapy
4.2. Microbiota and Chemotherapy
5. Future Directions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
BAL | Broncho-alveolar lavage |
BAX | Bcl-2-associated X protein |
CDA | Cytidine deaminase |
CDK1NB | Cyclin-dependent kinase inhibitor 1B |
COPD | Chronic obstructive lung disease |
CTLA-4 | Cytotoxic T-lymphocyte-associated protein 4 |
EC | endothelial cells |
ERK | Extracellular signal-regulated kinases |
GEMM | genetically engineered mouse models |
GZMB | Granzyme B |
Her2 | human epidermal growth factor receptor 2 |
FEV | Forced expiratory volume |
FMT | Fecal microbiota transplant |
ICI | Immune checkpoint inhibitor |
IFN-γ | Interferon gamma |
IL | Interleukin |
IPF | Idiopathic pulmonary fibrosis |
KEGG | Kyoto Encyclopedia of Genes and Genomes |
MAPK | Mitogen-activated protein kinase |
NF-κB-1 | Nuclear factor kappa B subunit 1 |
NSCLC | Non-small-cell lung cancer |
RCC | Renal cell carcinoma |
PARP1 | Poly [ADP-ribose] polymerase 1 |
PD-1 | Programmed cell death protein 1 |
PD-L1 | Programmed death-ligand 1 |
PFR1 | Perforin 1 |
PI3K | Phosphoinositide 3-kinase |
PRRs | Pattern recognition receptors |
PTPA | protein-tyrosine-phosphatase A |
TNF | Tumor necrosis factor |
STAT3 | Signal transducer and activator of transcription 3 |
TLR4 | Toll-like receptor 4 |
TNFa | Tumor necrosis factor alfa |
VEGF | Vascular endothelial growth factor |
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Bacterial Classification | Sampling Method | Association with Lung Cancer | Potential Mechanism of Association with Lung Cancer |
---|---|---|---|
Pseudomonas [24,25,26,27,28,29] | Lung explants, BAL, Brush specimen, lung tissues | Marked presence in lung adenocarcinoma | Associated with an increase in macrophage population and IFN-γ in BAL sample. Amplification of neutrophil elastase activity. Enhanced/diminished population associated with smoking |
Streptococcus [24,25,27,30,31,32,33,34] | Lung explants, BAL, Brush specimen, lung tissues | Marked presence in lung cancer, specifically adenocarcinoma, squamous cell carcinoma, and increased risk of hepatic metastasis from NSCLC Increased levels in the gut of small cell lung cancer patients | Enhanced ERK and PI3K pathway. Increased presence of Th17 cells and neutrophils. Enhanced/ diminished population in smokers |
Prevotella [24,25,30,31,32,33,34] | Lung explants, BAL, Brush specimen | Low presence in the gut of NSCLC patients. Marked presence in the gut of squamous cell carcinoma patients Marked presence in lung cancer and adenocarcinoma | Correlated to an inflammatory phenotype, including an enhanced Th17 lymphocyte and neutrophil response Enhancement of ERK and PI3K pathway |
Fusobacterium [25,31,32,33,35,36,37] | Lung explants, BAL, Brush specimen | Poor response in lung cancer to anti-PD-1 therapy if Fusobacterium is present in the airway. One of the most abundant specific bacterial community members detected in synchronous multiple primary lung cancer sMPLC lesions. | Fap2 protein of Fusobacterium inhibits natural killer cell killing by interacting with an inhibitory receptor present on all human NK cells and on various T cells (TIGIT receptor) |
Veillonella [24,25,27,31,38,39] | Lung explants, BAL, Brush specimen, lung tissues, saliva | Observed in both small cell lung cancer and adenocarcinoma | Correlated to an inflammatory phenotype, including an enhanced Th17 lymphocyte and neutrophil response. Most abundant agent driving dysbiosis and amplification of IL17, PI3K, MAPK, and ERK pathways in the airway transcriptome |
Prophyromonas [25,26,31,40,41] | Lung explants, BAL, Brush specimen | Higher P. gingivalis staining in carcinoma tissues of patients with small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma (35.00%, 26.89%, and 39.00%, respectively) compared to the adjacent lung tissues | Activation of cancer-associated transcription factors by modulating ATP-induced cytosolic, mitochondrial ROS, and antioxidant glutathione response through the inhibition of ATP/ P2X7-induced cell death by P. gingivalis. |
Neisseria [25,42] | Lung explants, BAL, Brush specimen, saliva | Reduced presence in lung cancer | Suppress cell growth |
Haemophilus [25,26,43] | Lung explants, BAL | Stimulates proliferation of early adenomatous lesions leading to alveolar adenomatous hyperplasia and adenocarcinoma | Upregulation of IL-17C and neutrophil infiltration. Can also promote metastatic progression in combination with cigarette smoke (8) |
Sphingomonas [26,27] | BAL, Brush specimen, lung tissues | Marked presence in adenocarcinoma | Associated with an increase in macrophage population and prominent IFN-γ population |
Acinetobacter [25,26,34,44] | Lung explants, BAL | Marked presence in lung cancer and adenocarcinoma | DNA methylation of CpG regions in the promoters of E-cadherin gene induced by A. baumannii transposase (Tnp) and down-regulation of this gene |
Staphylococcus [25,28,45] | Lung explants, BAL, Brush specimen, lung tissues | Marked presence in the gut of NSCLC patients responsive to Nivolumab | Lipoteichoic acid induced cellular proliferation and liberation of interleukin (IL)-8. |
Corynebacterium [25,26,31,46] | Lung explants, BAL, Brush specimen | No significant difference in microbiota composition between ground glass pulmonary nodules and normal tissues except in adenocarcinoma (AD) | - |
Lactobacillus [24,26,27,31] | BAL, Brush specimen, lung tissues | Low levels in the gut of NSCLC patients (8). High abundance in the gut of squamous cell carcinoma patients | Gut microbiota’s role in regulating the lung’s immune response. |
Actinobacillus [24,26,31,47] | Lung explants, BAL, saliva | Increase in the gut of lung cancer patients and commonly found in the lungs and sputum of lung cancer patients | Actinobacillus’ presence in the airway leads to chronic lung inflammation promoting the initiation and early development of lung cancer. |
Propionibacterium [26,47] | BAL | Marked presence in the gut of NSCLC patients responsive to Nivolumab Marked presence in squamous cell carcinoma | Gut microbiota’s role in regulating the lung’s immune response. |
Ralstonia [29,48] | Lung tissues | Marked presence in adenocarcinoma | Plays a role in impairing the tumor microenvironment’s immunity |
Megasphaera [39,49] | BAL | Marked presence in lung cancer patients | Promotes somatic cell genome instability via high levels of chromosomal aberrations (CAs) and micronuclei (MN) frequency seen in peripheral blood lymphocytes of patients with lung cancer |
Acidovorax [50,51] | Lung tissues | A marked presence in squamous cell carcinoma patients compared with adenocarcinoma. Specific taxa are more common in smokers with TP53 mutation | Degrades tobacco smoke compounds and thus promoting survival of transformed cells and subsequent tumor development. Malignant transformation of the lung epithelium via DNA damage and mutations in TP53, mediated by microbial toxins or reactive oxygen/nitrogen. |
Capnocytophaga [52,53,54] | Saliva | A marked increase in lungs of lung cancer patients compared to control | Stimulation of chronic inflammation, thus promoting the development of lung cancer, especially lung squamous cell carcinoma |
Cyanobacteria [52,55] | Lung tissue | A marked increase in lungs of adenocarcinoma patients | Cyanobacteria toxin microcystin is associated with reduced CD36 and increased levels of PARP1 |
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Bou Zerdan, M.; Kassab, J.; Meouchy, P.; Haroun, E.; Nehme, R.; Bou Zerdan, M.; Fahed, G.; Petrosino, M.; Dutta, D.; Graziano, S. The Lung Microbiota and Lung Cancer: A Growing Relationship. Cancers 2022, 14, 4813. https://doi.org/10.3390/cancers14194813
Bou Zerdan M, Kassab J, Meouchy P, Haroun E, Nehme R, Bou Zerdan M, Fahed G, Petrosino M, Dutta D, Graziano S. The Lung Microbiota and Lung Cancer: A Growing Relationship. Cancers. 2022; 14(19):4813. https://doi.org/10.3390/cancers14194813
Chicago/Turabian StyleBou Zerdan, Maroun, Joseph Kassab, Paul Meouchy, Elio Haroun, Rami Nehme, Morgan Bou Zerdan, Gracia Fahed, Michael Petrosino, Dibyendu Dutta, and Stephen Graziano. 2022. "The Lung Microbiota and Lung Cancer: A Growing Relationship" Cancers 14, no. 19: 4813. https://doi.org/10.3390/cancers14194813
APA StyleBou Zerdan, M., Kassab, J., Meouchy, P., Haroun, E., Nehme, R., Bou Zerdan, M., Fahed, G., Petrosino, M., Dutta, D., & Graziano, S. (2022). The Lung Microbiota and Lung Cancer: A Growing Relationship. Cancers, 14(19), 4813. https://doi.org/10.3390/cancers14194813