Exposure to diesel particulates induces an immunosuppressive microenvironment that promotes the progression of lung cancer

• Kras mutated mice exposed to DEP develop larger, more proliferative lung tumours. • Exposure to DEP recruits CD14 pos PMNs in lungs. • CD14 pos PMNs display suppressive features and induce T cell dysfunction. • DEP-induced recruitment of immunoregulatory PMNs might be relevant in humans. A comprehensive understanding of the mechanisms by which air pollutant exposure drives cancer progression remains incomplete. Particulate matter has been shown to induce genotoxicity and mutagenesis through oxidative stress both in vivo and in vitro . However, its impact on the pulmonary immune microenvironment and its role in modulating anti-tumour immune responses remains poorly characterized. Here, we report that chronic exposure to diesel exhaust particles (DEPs), a major component of PM2.5, induces an immunosuppressive lung microenvironment that promotes tumour progression in a KRAS-driven lung adenocarcinoma model ( Kras LSL-G12D/+ -Trp53 lox/lox or KP mice). This environment is characterized by the emergence of PMN-MDSC (CD14 pos PMNs) that exhibit NET formation and an immunosuppressive gene expression and functional profile. Additionally, we observed increased infiltration of regulatory T cells (Tregs), and upregulation of exhaustion/activation and immunosuppressive markers on T cells, factors that likely contribute to the increased tumour burden and enhanced tumour cell proliferation seen in DEP-exposed KP mice. Our study reveals how chronic DEP exposure reshapes the lung microenvironment in ways that may impair the ability to mount effective anti-tumour immune responses. These findings highlight the need for stronger public and occupational health policies aimed at reducing air pollution and its associated disease burden.