Abstract Tumor-associated macrophages (TAMs) are considered key determinants of breast cancer progression, yet the molecular mechanisms shaping their immunosuppressive phenotypes remain incompletely understood. The NOX2 enzyme of myeloid cells generates antimicrobial reactive oxygen species (ROS) in myeloid cells, but its potential contribution to macrophage programming within the tumor microenvironment is largely unknown. This study aimed at identifying the potential role of NOX2 in regulating