Velasco Walter V, Grimaldo Maria T, Karimi Nastaran, Clowers Michael J, Krishna Avantika, Wu Ranran, Ejaz Rahmah, Yuan Bo, Aguila Segundo Del, Bouchelkia Iman, Barragan Javier Eduardo Moreno, Larsen Katherine E, Rezai Yasmina, Khalaj Farbod, Mitra Kyler, Rodriguez Carlos Reyna, Millares Ricardo, de Anda Angelica Baca, Castro-Pando Susana, Karandikar Umesh C, Petrosino Joseph F, McAllister Florencia, Kadara Humam, Ostrin Edwin J, Fahrmann Johannes F, Hoffman Kristi Louise, Moghaddam Seyed Javad
Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, United States.
Neoplasia. 2025 Jun 13;67:101185. doi: 10.1016/j.neo.2025.101185.
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.
尽管电子烟烟雾（ECV）的使用引发了新的公共卫生问题，但其对肺癌的影响仍知之甚少。我们在肺腺癌小鼠模型中评估了ECV对肺肿瘤发生的影响。将小鼠每天暴露于室内空气、可燃香烟烟雾（CCS）或ECV中2小时，持续8周，之后采集肺样本并研究不同的结果。我们发现，CCS而非ECV导致肿瘤负担显著增加。对暴露于CCS和ECV的肺进行免疫表型分析显示出明显的促肿瘤免疫抑制表型，其特征是CD4+IFNγ+和CD8+GZMB+T细胞显著减少，同时CD4+FOXP3+调节性T细胞增加。然而，在暴露于CCS和ECV的肺之间观察到髓样细胞的差异变化。对匹配的粪便和肺样本进行微生物组分析显示，肺假单胞菌门的相对丰度存在差异，而肠道芽孢杆菌门，特别是Turicibacter和艾氏杆菌属在CCS和ECV作用下增加。我们得出结论，在所应用的方案下，暴露于CCS和ECV都会导致促肿瘤免疫抑制性肺微环境，尽管程度不同且表型略有差异，这可能解释了它们对肿瘤负担的不同影响，值得进一步研究。
