Leveraging specimens from a prospective neoadjuvant niraparib monotherapy trial in treatment-naive, high-grade serous ovarian cancer, we integrated PhenoCycler-Fusion spatial profiling, scRNA-Seq, and multiplex immunohistochemistry to identify 2 therapeutic-modulated cellular neighborhoods: an IFN+ tumor cell-enriched niche that expands in resistant lesions and a niche enriched in tumor-associated macrophage (TAM) that persists but acquires enhanced immunosuppressive features. The gene discussed is IFNA1; the disease is neoplasm.