Single-nucleus transcriptomics reveals an early-relapse-associated epithelial–myeloid–T cell niche in advanced high-grade serous ovarian cancer

Abstract

Early relapse remains a major clinical challenge in advanced HGSOC, but the tumor microenvironmental features associated with relapse timing remain poorly defined. Here, we performed snRNA-seq on treatment-naive tumors from patients with advanced HGSOC, including STDFS ( n = 4) and LTDFS ( n = 6), profiling 120,495 nuclei. Integrative analyses of cell composition, transcriptional programs, and intercellular communication were complemented by validation using TCGA-OV bulk RNA-seq and mIF in an independent cohort ( n = 41). STDFS tumors showed coordinated enrichment of stem-like CD8 + T cells, SPP1 + macrophages, and CD47 + epithelial cells. Ligand–receptor inference predicted enhanced communication among these populations, including SPP1–integrin and CD47–SIRPA signaling, while mIF-based spatial analysis confirmed their increased proximity in STDFS tumors. Across TCGA-OV and the validation cohort, higher abundance of these cell states, both individually and jointly, was associated with shorter DFS. Together, these findings identify a relapse-associated immunoregulatory niche marked by the coordinated accumulation and spatial organization of stem-like CD8 + T cells, SPP1 + macrophages, and CD47 + epithelial cells, providing a transcriptomic and spatial framework for understanding early relapse and refining prognostic biomarker discovery in advanced HGSOC.