Myeloperoxidase promotes a tumorigenic microenvironment in non-small cell lung cancer

Myeloperoxidase (MPO) is a heme peroxidase that is mainly expressed and secreted by neutrophils. MPO's role in inflammatory diseases has been highlighted in recent years, but its role in tumor development remains unclear. Therefore, we investigated the role of MPO in non-small cell lung cancer (NSCLC). In silico analysis revealed a survival benefit in patients with NSCLC and low MPO expression. Furthermore, a syngeneic tumor model using MPO knockout (KO) mice revealed that mice lacking MPO had lower tumor growth than controls. The reduction in tumor size was accompanied by an increase in lymphoid populations, including natural killer cells and CD8⁺ T cells, suggesting a shift to a more anti-tumorigenic immune environment in MPO-KO mouse tumors. The T cell induced interferon-gamma (IFN-γ) expression was increased in MPO-KO tumors, indicating increased tumoricidal activity. CD8 depletion abolished the previously observed reduction in tumor size in MPO-KO mice, indicating that CD8⁺ T cells play an important role. In vitro, T cells treated with MPO showed reduced proliferation and IFN-γ expression. Furthermore, MPO associated directly with T cells. Interestingly, MPO⁺ lymphocytes, including CD8⁺ T cells, were found in tumor samples from patients with NSCLC. Our findings suggest that MPO plays an immunosuppressive role in NSCLC.