Polyethylene terephthalate microplastics induce immune evasion and malignant remodeling in breast cancer through multi-omics-identified immune checkpoints.

Polyethylene terephthalate (PET) microplastics (MPs) have emerged as a significant environmental contaminant with potential adverse effects on human health, particularly in cancer biology. This study investigates the molecular and immunological mechanisms underlying the influence of PET-MPs on breast cancer (BC) progression. Employing an integrative approach that combines bioinformatics analysis of public cancer databases (TCGA), molecular docking simulations, and in vitro experiments, we identified four immune-related genes-CCL19, KLRB1, CD40LG, and IGLL5-that are potentially modulated by PET-MPs. Molecular docking indicated that bis(2-hydroxyethyl) terephthalate (BHET), a key PET oligomer, binds with high affinity to these proteins, suggesting that PET-MPs may alter immune homeostasis within the tumor microenvironment (TME). Additionally, PET-MPs induced a pro-inflammatory cytokine response, including elevated IL-6 and TNF-α secretion, which could promote tumor progression. Our findings further suggest that PET-MPs may enhance BC cell proliferation and survival through immune modulation. However, limitations include the lack of immune cell co-culture models and in vivo validation. This study provides essential insights into the immunotoxicity of PET-MPs and highlights the need for further research to explore their direct and indirect effects on cancer development.