1. Spatiotemporal architecture of immune cells and cancer-associated fibroblasts in high-grade serous ovarian carcinoma
- Author
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Xu, Alexander M, Haro, Marcela, Walts, Ann E, Hu, Ye, John, Joshi, Karlan, Beth Y, Merchant, Akil, and Orsulic, Sandra
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Ovarian Cancer ,Cancer ,Rare Diseases ,Prevention ,Female ,Humans ,Cancer-Associated Fibroblasts ,Neoplasm Recurrence ,Local ,Antineoplastic Agents ,Ovarian Neoplasms ,Recurrence ,Tumor Microenvironment - Abstract
High-grade serous ovarian carcinoma (HGSOC), the deadliest form of ovarian cancer, is typically diagnosed after it has metastasized and often relapses after standard-of-care platinum-based chemotherapy, likely due to advanced tumor stage, heterogeneity, and immune evasion and tumor-promoting signaling from the tumor microenvironment. To understand how spatial heterogeneity contributes to HGSOC progression and early relapse, we profiled an HGSOC tissue microarray of patient-matched longitudinal samples from 42 patients. We found spatial patterns associated with early relapse, including changes in T cell localization, malformed tertiary lymphoid structure (TLS)-like aggregates, and increased podoplanin-positive cancer-associated fibroblasts (CAFs). Using spatial features to compartmentalize the tissue, we found that plasma cells distribute in two different compartments associated with TLS-like aggregates and CAFs, and these distinct microenvironments may account for the conflicting reports about the role of plasma cells in HGSOC prognosis.
- Published
- 2024