Comparative effects of combustible cigarette versus electronic cigarette exposures on KRAS mutant lung cancer promotion

Despite the emerging public health concern related to the use of electronic cigarette vapors (ECV), its impact on lung cancer is poorly understood. We assessed the effect of ECV on lung tumorigenesis in a mouse model of lung adenocarcinoma. Mice were exposed to either room air, combustible cigarette smoke (CCS), or ECV 2 hours daily for 8 weeks at which lung samples were harvested and studied for different outcomes. We found that CCS, but not ECV, led to a significant increase in tumor burden. Immunophenotyping of both CCS- and ECV-exposed lungs displayed pronounced pro-tumor immunosuppressive phenotypes, characterized by significantly decreased CD4+ IFNγ+ and CD8+ GZMB+ T cells along with an elevated CD4+ FOXP3+ regulatory T cells. However, differential changes in myeloid cells were observed between CCS and ECV-exposed lungs. A microbiome profiling of matched stool and lung samples showed differences in the relative abundance of lung Pseudomonadotas, while gut Bacillota, particularly Turicibacter, and Ileibacterium were increased by CCS and ECV. We conclude that both CCS and ECV exposure under the applied regimen lead to a protumor immune suppressive lung microenvironment although with different magnitudes and slightly different phenotypes that might explain their differential effects on tumor burden warranting further studies.

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Publication Details

Journal
Neoplasia
Published
2025-06-13
DOI
https://doi.org/10.1016/j.neo.2025.101185
Primary Topic
Lung Cancer Treatments and Mutations
Type
article
Field-Weighted Citation Impact
0.00
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article

Comparative effects of combustible cigarette versus electronic cigarette exposures on KRAS mutant lung cancer promotion

Ranran Wu, Umesh C. Karandikar, Seyed Javad Moghaddam, Nastaran Karimi et al.
Neoplasia
Lung Cancer Treatments and Mutations
article

Comparative effects of combustible cigarette versus electronic cigarette exposures on KRAS mutant lung cancer promotion

Ranran Wu, Umesh C. Karandikar, Seyed Javad Moghaddam, Nastaran Karimi, Joseph F. Petrosino, Florencia McAllister, K. Mitra, Javier Eduardo Moreno Barragan, Humam Kadara, Walter V. Velasco, Edwin J. Ostrin, Michael J. Clowers, Bo Yuan, Susana Castro-Pando, Johannes F. Fahrmann, Kristi L. Hoffman, Iman Bouchelkia, Maria T. Grimaldo, Yasmina H. Rezai, Farbod Khalaj, Angélica Baca De Anda, María Cecilia Rodríguez, Avantika Krishna, Segundo W Del Aguila, Katherine E. Larsen, Rahmah Ejaz, Ricardo Millares
article en

Abstract

Despite the emerging public health concern related to the use of electronic cigarette vapors (ECV), its impact on lung cancer is poorly understood. We assessed the effect of ECV on lung tumorigenesis in a mouse model of lung adenocarcinoma. Mice were exposed to either room air, combustible cigarette smoke (CCS), or ECV 2 hours daily for 8 weeks at which lung samples were harvested and studied for different outcomes. We found that CCS, but not ECV, led to a significant increase in tumor burden. Immunophenotyping of both CCS- and ECV-exposed lungs displayed pronounced pro-tumor immunosuppressive phenotypes, characterized by significantly decreased CD4+ IFNγ+ and CD8+ GZMB+ T cells along with an elevated CD4+ FOXP3+ regulatory T cells. However, differential changes in myeloid cells were observed between CCS and ECV-exposed lungs. A microbiome profiling of matched stool and lung samples showed differences in the relative abundance of lung Pseudomonadotas, while gut Bacillota, particularly Turicibacter, and Ileibacterium were increased by CCS and ECV. We conclude that both CCS and ECV exposure under the applied regimen lead to a protumor immune suppressive lung microenvironment although with different magnitudes and slightly different phenotypes that might explain their differential effects on tumor burden warranting further studies.

NeoplasiaVol. 67
The University of Texas MD Anderson Cancer Center (US), Baylor College of Medicine (US)
Openalex Percentile: Top 77%
Lung Cancer Treatments and Mutations
DOIOpen Access PDFOpenAlex
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