Cigarettes or vapes, pick your poison

E-cigarette use, or vaping, has grown in popularity and with it, so has the availability of mods and vape flavors to meet every style and palette. But is this popular habit actually harmful? “Vaping has been used as an approach for smoking cessation to avoid the exposure to carcinogens,” stated Dr. Lawrence Fong, the newly appointed Scientific Director of the Immunotherapy Integrated Research Center and Professor of the Translational Science and Therapeutics Division at Fred Hutchinson Cancer Center. However, “our work indicates that vaping may not be as benign as previously believed.” Dr. Fong recently moved to Fred Hutch from UCSF where the work described here was carried out. The Fong lab used cancer cell lines and pre-clinical mouse models of several cancer types—melanoma, colorectal cancer, and prostate cancer—to study the effects of E-Liquids on cancer. E-Liquids contain inert ingredients propylene glycol (PG), an odorless and flavorless liquid used in anti-freeze, as well as vegetable glycerin (VG) that upon heating, enhance aerosolization of nicotine or cannabis for inhalation. The researchers found that these inert ingredients alone or with nicotine can increase metastasis of cancer to the lung and suppress the immune system which is critical for immunotherapy-based treatments for cancer. Their findings were published in Frontiers in Immunology.

It might seem logical that inhaling any foreign substance into the lungs could be harmful, but for those hoping to find an alternative to cigarettes, cigars or pipes, vaping might seem like a safe alternative. The E-Liquids that contain PG/VG inactive ingredients with nicotine or cannabis are not carcinogens per se but rigorous testing of PG/VG alone or in combination with nicotine in models of cancer has been limited. For this reason, the Fong lab wanted to learn how the components of E-Liquids—PG/VG and nicotine—influence metastasis and the tumor microenvironment.

Metastasis, the spread of cancer from its original site to other parts of the body, is a key factor in cancer mortality. To understand how PG/VG alone or in combination with nicotine might affect cancer cell migration, the researchers conducted studies using cancer cells and pre-clinical mouse models of cancer. One assay used is called a scratch test. This assay measures the movement of cells back to a cleared area following a scratch made through a single layer of cells. The researchers found that colorectal cancer cells migrated back into the cleared area much faster when cells were treated with PG/VG as compared to untreated cells. In mouse models of melanoma, colorectal and prostate cancer metastasis, they recorded increased cancer metastases to the lung—a common site of cancer metastasis—in animals that received tail vein injections of cancer cells preconditioned with PG/VG alone or combined with nicotine as compared to injected cancer cells without preconditioning treatments. Furthermore, the colorectal cancer metastases in the lung were more aggressive—increased number of tumor nodules and reduced survival of mouse model—for preconditioned cancer cells implanted into the mouse or through whole mouse exposure in vaping chamber as compared to their respective controls in which cancer cells or mice were not exposed to PG/VG.

Cancer progression is also impacted by the immune system. Specifically, immune cells play important anti-tumor roles in the tumor microenvironment and can be harnessed to target and kill cancer cells (e.g. immunotherapy). For this reason, the researchers also investigated the role of PG/VG on immune cell activity in the tumor microenvironment. Two main signatures were observed under PG/VG plus nicotine conditions, T cell exhaustion and increased inflammation, both of which exacerbate cancer progression. Together, “we show that the inert carrier used in vaping, PG/VG, can be immunosuppressive and enhance tumor progression in pre-clinical models,” summarized Dr. Fong.

These findings specifically caution vaping practices by cancer patients since E-Liquid components were shown to exacerbate cancer progression in these models of disease. Furthermore, the lead author Dr. Marcel Arias Badia shared two lingering thoughts following this published work that support continued study of how E-Liquids affect cancer initiation and disease progression. First, “we believe the appearance of metastasis upon exposure to e-cigarettes in preclinical models that don’t usually metastasize warrants a deeper study of the potential triggering mechanisms following e-cigarette consumption leading to cancer dissemination” and second, “we hope our study contributes to better understanding the associated risks of consuming e-cigarettes for cancer patients, especially those treated with immunotherapy.” Dr. Arias Badia explained that multi-omic datasets of cancer patients stratified by E-cigarette usage can be analyzed to determine the clinical impact of E-cigarette usage on elevating risk of cancer development and progression. These research directions will clarify how E-Liquid contents exacerbate cancer progression and provide support for whether E-cigarette usage increases risk of cancer development in patients.

The spotlighted research was funded by the National Institutes of Health, the FDA Center for Tobacco Products, and the UCSF Cancer Center.

Fred Hutch/University of Washington/Seattle Children's Cancer Consortium member Dr. Lawrence Fong contributed to this work.

Arias-Badia M, Pai CS, Chen P, Chang A, Lwin YM, Srinath A, Gotts JE, Glantz SA, Fong L. 2024. E-cigarette exposure disrupts antitumor immunity and promotes metastasis. Front Immunol. 15:1444020.