E-cigarette exposure disrupts antitumor immunity and promotes metastasis

Area of Science:

• Oncology
• Immunology
• Toxicology

Background:

• Electronic cigarettes (e-cigarettes) are perceived as low-risk for cancer due to non-carcinogenic liquid components.
• Preclinical models are used to investigate the oncogenic potential of e-cigarette constituents.

Purpose of the Study:

• To analyze the effects of propylene glycol/vegetable glycerin (PG/VG) and nicotine on tumor development.
• To investigate the impact of e-cigarette components on tumor aggressiveness, metastasis, and the tumor microenvironment.

Main Methods:

• In vitro migration assays were performed to assess tumor cell migration.
• In vivo preclinical models were used to evaluate tumor development and immune responses following PG/VG and nicotine exposure.
• Flow cytometry and immunohistochemistry were employed to analyze immune cell infiltration and immune checkpoint expression.

Main Results:

• PG/VG promoted tumor cell migration and led to more aggressive, metastatic, and immunosuppressive tumors, effects exacerbated by nicotine.
• Exposure to PG/VG and nicotine increased susceptibility to tumor development, characterized by proinflammatory macrophages (IL-6, TNFα).
• E-cigarette exposure elevated immune checkpoints (CTLA4, PD-1) on T cells, and anti-CTLA4 therapy reduced metastasis.

Conclusions:

• Major e-cigarette liquid components (PG/VG and nicotine) can promote tumor development and metastasis.
• E-cigarette use may induce immunosuppression, contributing to a more aggressive tumor microenvironment.
• Targeting immune checkpoints like CTLA4 shows potential for treating e-cigarette-associated tumor progression.