Chronic exposure to waterpipe smoke elicits immunomodulatory and carcinogenic effects in the lung
Cancer Research
; 82(12), 2022.
Article
Dans Anglais
| EMBASE | ID: covidwho-1986460
ABSTRACT
Effects of waterpipe smoking on lung pathobiology and carcinogenesis remain sparse despite the worldwide emergence of this tobacco vector as a socially acceptable form of smoking, particularly among the youth. To address this gap, we investigated the effects of chronic waterpipe smoke (WPS) exposure on lung pathobiology, host immunity, and tumorigenesis using both an experimental animal model and an exploratory observational analysis of human waterpipe smokers and non-smokers. Mice exposed to increasing doses of WPS (once or five times per week for 20 weeks), through an exclusively devised exposure system for this study, were more prone to develop lung tumors compared to control-air exposed littermates. This effect was accompanied by various pro-tumor immune phenotypes, including increased IL-17A+ levels in T/B cells as well as elevated expression of the immune checkpoint PD-L1 and the pro-inflammatory cytokine IL-1β in myeloid cells. While flow cytometry analysis revealed increased CD4 and CD8 T cell infiltration in WPSexposed mice, gene signatures of cytotoxic and expanded immune response were, conversely, decreased in animals exposed to heavy WPS relative to control air. Interestingly, mice heavily exposed to WPS exhibited increased expression of Tmprss4, Cd55, and Ace2, cell receptors and mediators of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and, thus, COVID-19 pathogenesis. We also perform RNA-sequencing analysis of bronchial airway epithelial brushings of cancer-free waterpipe smokers and non-smokers undergoing diagnostic bronchoscopy. Transcriptomes of normal airway cells in waterpipe smokers, relative to waterpipe non-smokers, harbored gene programs that were associated with poor clinical outcomes in lung adenocarcinoma (LUAD) patients, alluding to a WPS-associated molecular injury, like that established in response to cigarette smoking. Overall, our analyses demonstrate immunomodulatory and carcinogenic effects of WPS on the murine and human lung. Our study also shows that WPS exposure leads to a field of injury that may be associated with increased risk for lung cancer. This study is unique for interrogating carcinogenic effects of chronic exposure to WPS with the longest, to our knowledge, follow-up time in vivo. Our findings accentuate the need for additional studies that can guide evidence-based policies to counteract shortfalls in public health control of waterpipe smoking.
angiotensin converting enzyme 2; CD4 antigen; cytokine; decay accelerating factor; endogenous compound; interleukin 1beta; programmed death 1 ligand 1; transcriptome; adult; airway cell; animal cell; animal experiment; animal model; B lymphocyte; bone marrow cell; bronchoscopy; cancer patient; CD8+ T lymphocyte; cell infiltration; cigarette smoking; clinical outcome; conference abstract; controlled study; coronavirus disease 2019; exploratory research; flow cytometry; follow up; gene expression; hookah; human; immune response; in vivo study; injury; long term exposure; lung adenocarcinoma; lung cancer; male; mouse; non-smoker; nonhuman; outcome assessment; phenotype; protein expression; public health; RNA sequencing; Severe acute respiratory syndrome coronavirus 2; smoke; smoking; water pipe smoking
Texte intégral:
Disponible
Collection:
Bases de données des oragnisations internationales
Base de données:
EMBASE
Type d'étude:
Études expérimentales
langue:
Anglais
Revue:
Cancer Research
Année:
2022
Type de document:
Article
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