电子烟暴露破坏抗肿瘤免疫并促进转移
E-cigarette exposure disrupts antitumor immunity and promotes metastasis
影响因子:5.90000
分区:医学2区 / 免疫学2区
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
摘要
由于电子烟液的成分不是致癌物，因此人们认为电子卷烟（电子烟）会构成癌症的低风险。我们分析了两个主要成分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在迁移分析中促进了肿瘤细胞的迁移，并在体内促进了更具侵略性，转移性和免疫抑制性肿瘤，并因尼古丁的存在而加剧。小鼠对PG/VG和尼古丁的全身暴露使动物更容易受到表达IL-6和TNFα的高频浸润促炎巨噬细胞的肿瘤。此外，电子烟暴露的小鼠中肿瘤浸润和循环的T细胞显示，包括CTLA4和PD-1在内的免疫检查点水平增加。抗CTLA4抗体的治疗能够消除转移，而对其在暴露小鼠中诱导肿瘤消退的能力没有不利影响。这些发现表明，用于电子烟液中的主要成分会通过诱导的免疫抑制影响肿瘤的发育。
Abstract
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.