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Background <p>Over the years, lung cancer incidence in never-smokers has been rising. Air pollution is a non-smoking-related factor that promotes lung cancer progression. Particulate matter 2.5 (PM2.5) is a component of air pollution that is associated with a type 2 immune response mediated by group 2 innate lymphoid cells (ILC2) and T helper 2 (Th2) cells. Furthermore, PM2.5 can activate fibroblasts, induce the secretion of collagen, and contribute to the development of lung fibrosis. Although type 2 immune response and lung fibrosis are described as pro-tumorigenic in lung cancer, whether PM2.5-driven type 2 immune response and/or lung fibrosis promote lung cancer tumorigenesis in mouse models of lung cancer remains unclear. This study investigated the impact of PM2.5 on the type 2 immune response, lung fibrosis, and lung cancer tumorigenesis in vivo.</p> Methods <p>We treated EGFR and KRAS/Trp53 mouse models of LUAD intranasally with PM2.5, analyzed lung tumor burden and lung fibrosis by histology, and changes in type 2 immune cell (ILC2, Th2) and CAF markers by flow cytometry. Different durations of PM2.5 treatment (3-week short-term vs. 6-week long-term), experimental time points (10&#xa0;weeks vs. 15&#xa0;weeks), and intervals between the onset of EGFR and KRAS/Trp53 mutations and first exposure to PM2.5 (3&#xa0;days vs. 4&#xa0;weeks delayed) were assessed. Unpaired t-test and One-way ANOVA statistical tests were utilized.</p> Results <p>We found that PM2.5 did not significantly impact lung tumor burden in EGFR and KRAS/Trp53 mouse models of LUAD. Notably, PM2.5 did not significantly affect the type 2 immune response mediated by ILC2 and Th2 cells. However, long-term exposure to PM2.5 or delayed treatment with PM2.5 significantly increased the abundance of CD90.2<sup>+</sup> CAFs in lung cancer without impacting lung cancer burden.</p> Conclusions <p>In summary, while PM2.5 did not significantly impact EGFR and KRAS/Trp53 lung tumor burden or the type 2 immune response, long-term or delayed exposure to PM2.5 promoted CD90.2<sup>+</sup> CAFs in vivo. This study demonstrates that preclinical modeling of PM2.5-driven LUAD requires further validation and consideration of confounding variables to reflect air pollution-associated LUAD observed in humans.</p>

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Impact of particulate matter 2.5 on a mouse model of lung adenocarcinoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月21日

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  • Elif Irmak Bektas,
  • Aftab Alam,
  • Sharon Senchanthisai,
  • Shyamananda Singh Mayengbam,
  • Emily Mackey,
  • Emily Spitz,
  • Shamshad Alam,
  • Boyko Atanassov,
  • David W. Goodrich,
  • Prasenjit Dey

摘要

Background

Over the years, lung cancer incidence in never-smokers has been rising. Air pollution is a non-smoking-related factor that promotes lung cancer progression. Particulate matter 2.5 (PM2.5) is a component of air pollution that is associated with a type 2 immune response mediated by group 2 innate lymphoid cells (ILC2) and T helper 2 (Th2) cells. Furthermore, PM2.5 can activate fibroblasts, induce the secretion of collagen, and contribute to the development of lung fibrosis. Although type 2 immune response and lung fibrosis are described as pro-tumorigenic in lung cancer, whether PM2.5-driven type 2 immune response and/or lung fibrosis promote lung cancer tumorigenesis in mouse models of lung cancer remains unclear. This study investigated the impact of PM2.5 on the type 2 immune response, lung fibrosis, and lung cancer tumorigenesis in vivo.

Methods

We treated EGFR and KRAS/Trp53 mouse models of LUAD intranasally with PM2.5, analyzed lung tumor burden and lung fibrosis by histology, and changes in type 2 immune cell (ILC2, Th2) and CAF markers by flow cytometry. Different durations of PM2.5 treatment (3-week short-term vs. 6-week long-term), experimental time points (10 weeks vs. 15 weeks), and intervals between the onset of EGFR and KRAS/Trp53 mutations and first exposure to PM2.5 (3 days vs. 4 weeks delayed) were assessed. Unpaired t-test and One-way ANOVA statistical tests were utilized.

Results

We found that PM2.5 did not significantly impact lung tumor burden in EGFR and KRAS/Trp53 mouse models of LUAD. Notably, PM2.5 did not significantly affect the type 2 immune response mediated by ILC2 and Th2 cells. However, long-term exposure to PM2.5 or delayed treatment with PM2.5 significantly increased the abundance of CD90.2+ CAFs in lung cancer without impacting lung cancer burden.

Conclusions

In summary, while PM2.5 did not significantly impact EGFR and KRAS/Trp53 lung tumor burden or the type 2 immune response, long-term or delayed exposure to PM2.5 promoted CD90.2+ CAFs in vivo. This study demonstrates that preclinical modeling of PM2.5-driven LUAD requires further validation and consideration of confounding variables to reflect air pollution-associated LUAD observed in humans.