Epigenetic Rewiring of Immune Checkpoints in Pollution-Driven Lung Adenocarcinoma: An In Vitro and In Vivo Translational Study

• Authors: Elizabeth Benjamin Ekpo , Peter Ekanem
• Languages of publication: EN

Abstracts

EN

Air pollution has been increasingly recognized as a major risk factor for lung adenocarcinoma, yet the molecular mechanisms linking exposure to carcinogenesis remain unclear. Recent studies suggest that fine particulate matter (PM2.5) can alter epigenetic landscapes, particularly through DNA methylation and histone modification, thereby influencing immune regulation. This study investigated how pollution exposure can induce epigenetic rewiring of the immune checkpoint gene PD-L1, leading to impaired immune recognition and tumor progression. Lung adenocarcinoma cell lines were exposed to PM2.5 extracts, and methylation patterns were analyzed using bisulfite sequencing. The expression of PD-L1 and related immune genes was quantified by qPCR, and reactivation assays using histone deacetylase (HDAC) inhibitors were performed. Complementary in vivo studies were conducted in Wistar rats exposed to PM2.5 for six weeks to assess tissue-level alterations. Results demonstrated that PM2.5 exposure significantly increased DNA methylation at CpG islands within the PD-L1 promoter, reducing gene expression and T-cell activation capacity. Treatment with epidrugs such as valproic acid reversed methylation changes and restored immune function. The findings provide mechanistic insight into how environmental pollutants contribute to immune evasion in cancer and suggest potential therapeutic intervention through epigenetic modulation.

Keywords

EN

DNA methylation; PD-L1; PM2.5; T-cell activation; Wistar rat; air pollution; epidrugs; epigenetics; immune checkpoint; lung adenocarcinoma

Discipline

• BIOCHEMISTRY: BIOCHEMISTRY

• Publisher: Scientific Publishing House „DARWIN”
• Journal: World News of Natural Sciences
• Year: 2025
• Volume: 63
• Issue: 2
• Pages: 385-393

Contributors

author

Elizabeth Benjamin Ekpo

• Department of Biochemistry, University of Calabar, Calabar, Cross River State, Nigeria

author

Peter Ekanem

• Department of Pathology Laboratory, General Hospital, Calabar, Cross River State, Nigeria

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• Document Type: article