HRD‐Driven Reprogramming of Macrophage Function and Spatial Architecture in High‐Grade Serous Ovarian Cancer

High‐grade serous ovarian cancer (HGSOC) exhibits homologous recombination deficiency (HRD), but its impact on the immune microenvironment remains unclear. Using single‐cell RNA sequencing, spatial transcriptomic inference, and survival analyses, we characterized 166,895 macrophages across HRD subtypes: functional BRCA1/2 inactivation (FBI), HRD‐Del (deletions), and HRD‐Dup (duplications). FBI macrophages showed lipid metabolism enrichment (S100A8, CD36), HRD‐Del macrophages upregulated antigen presentation (HLA‐DQA1, HLA‐DPB1), and HRD‐Dup macrophages displayed interferon‐stimulated gene expression (ISG15, MX1). Six macrophage subtypes (C1Q, FCN1, MARCO, MKI67, MMP9, S100A9) exhibited distinct spatial distributions and functions. MKI67+ macrophages correlated with improved survival, while C1Q + subsets predicted worse outcomes. HRD‐Dup tumors with high macrophage signatures had better survival, suggesting a favorable immune landscape. Our findings reveal HRD‐driven macrophage reprogramming as a key determinant of immune microenvironment composition and clinical outcomes, supporting HRD‐specific macrophage‐targeted therapies for HGSOC.