研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

电子烟暴露会破坏抗肿瘤免疫力并促进转移。

E-cigarette exposure disrupts antitumor immunity and promotes metastasis.

发表日期:2024
作者: Marcel Arias-Badia, Chien-Chun Steven Pai, PeiXi Chen, Anthony Chang, Yee May Lwin, Aahir Srinath, Jeffrey E Gotts, Stanton A Glantz, Lawrence Fong
来源: Cell Death & Disease

摘要:

电子烟被认为患癌症的风险较低,因为电子烟液的成分不是致癌物质。我们分析了两种主要成分 PG/VG 和尼古丁对临床前模型中肿瘤发展的影响。我们发现,PG/VG 在迁移测定中促进肿瘤细胞迁移,并导致体内肿瘤更具侵袭性、转移性和免疫抑制性,尼古丁的存在会加剧这种情况。小鼠全身暴露于 PG/VG 和尼古丁使动物更容易患上表达 IL-6 和 TNFα 的浸润促炎巨噬细胞的肿瘤。此外,暴露于电子烟的小鼠体内的肿瘤浸润和循环 T 细胞显示出包括 CTLA4 和 PD-1 在内的免疫检查点水平增加。使用抗 CTLA4 抗体治疗能够消除转移,并且不会对其诱导暴露小鼠肿瘤消退的能力产生不利影响。这些发现表明,电子烟液中使用的主要成分可以通过诱导免疫抑制来影响肿瘤的发展。版权所有 © 2024 Arias-Badia、Pai、Chen、Chang、Lwin、Srinath、Gotts、Glantz 和 Fong。
Electronic cigarettes (e-cigarettes) are thought to pose low risk of cancer because the components of e-cigarette liquid are not carcinogens. We analyzed the effects of the two major components, PG/VG and nicotine, on tumor development in preclinical models. We found that PG/VG promoted tumor cell migration in migration assays and contributed to more aggressive, metastatic, and immunosuppressive tumors in vivo, aggravated by the presence of nicotine. Whole body exposure of mice to PG/VG and nicotine rendered animals more susceptible to developing tumors with high frequencies of infiltrating proinflammatory macrophages expressing IL-6 and TNFα. Moreover, tumor-infiltrating and circulating T cells in e-cigarette exposed mice showed increased levels of immune checkpoints including CTLA4 and PD-1. Treatment with anti-CTLA4 antibody was able to abrogate metastasis with no detrimental effects on its ability to induce tumor regression in exposed mice. These findings suggest that the major components used in e-cigarette fluid can impact tumor development through induced immunosuppression.Copyright © 2024 Arias-Badia, Pai, Chen, Chang, Lwin, Srinath, Gotts, Glantz and Fong.