학술논문

Spatiotemporal architecture of immune cells and cancer-associated fibroblasts in high-grade serous ovarian carcinoma
Document Type
article
Source
Science Advances. 10(16)
Subject
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
Language
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.