Abstract 399P
Background
COPD is a major risk factor for lung cancer, with chronic inflammation, immune dysregulation, and tissue remodeling contributing to tumor initiation. Microplastics (MPs), as environmental pollutants, may exacerbate these processes, but their impact on tumor-promoting microenvironments in COPD remains unclear.
Methods
scRNA-seq was performed on lung tissues from Normal, COPD, Normal+MPs, and COPD+MPs groups to analyze cellular dynamics and pathway activity. Functional experiments included flow cytometry, cytokine profiling (ELISA), vascular permeability assays, and organoid-based epithelial repair studies. Western blot and immunostaining assessed TGF-β signaling and ECM remodeling.
Results
MP exposure exacerbated COPD-associated inflammation and tissue remodeling, creating a tumor-permissive microenvironment: Immune: scRNA-seq revealed increased Gpnmb+ alveolar and Adgre5+ interstitial macrophages, alongside elevated CD4+ T cell recruitment and CD8+ T cell exhaustion in COPD+MPs. Flow cytometry confirmed significant increases in PD-1+/Tim-3+CD8+T cells and IL-6/TGF-β levels in BALF, suggesting immune suppression and chronic inflammation. Epithelial remodeling: AT2 cell populations critical for lung repair were significantly reduced in COPD+MPs, with Sftpc and Sox9 expression downregulated. Organoid experiments demonstrated impaired epithelial regeneration under MP exposure, with reduced organoid size and differentiation efficiency. Vascular and ECM changes: MPs disrupted endothelial function, increasing vascular permeability as shown by FITC-albumin leakage. Pro-fibrotic fibroblasts upregulated ECM remodeling genes and Mmp9 expression, validated byWestern blot and immunofluorescence. Signaling: COPD+MPs showed enhanced TGF-β signaling, enhanced p-Smad2/3 expression localized to macrophages and fibroblasts, driving chronic fibrosis.
Conclusions
Microplastic exposure intensifies chronic inflammation, immune dysregulation, and tissue remodeling in COPD, fostering a tumor-promoting environment. These findings link COPD pathology to mechanisms of lung cancer initiation and underscore the need to address environmental pollutants to reduce cancer risk.
Funding
Has not received any funding
Disclosure
All authors have declared no conflicts of interest.