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

Frontiers in Immunology

影响因子:5.9

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

DOI: 10.3389/fimmu.2024.1444020

摘要

电子烟（e-cigarettes）被认为具有较低的癌症风险，因为电子烟液的成分不被认为是致癌物。我们分析了两种主要成分——PG/VG和尼古丁对预临床模型中肿瘤发展的影响。结果发现，PG/VG促进肿瘤细胞迁移，并在体内导致更具侵袭性、转移性和免疫抑制性的肿瘤，尼古丁的存在进一步加剧了这种效应。全身暴露的老鼠在PG/VG和尼古丁的影响下，更易于发展出浸润有IL-6和TNFα的促炎性巨噬细胞高频率的肿瘤。此外，电子烟暴露组的肿瘤浸润T细胞和循环T细胞中免疫检查点（包括CTLA4和PD-1）的表达升高。使用抗CTLA4抗体能有效阻断转移，同时不影响其在暴露动物中诱导肿瘤退化的能力。这些发现表明，电子烟液中的主要成分可能通过诱导免疫抑制影响肿瘤发生。

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.