Spatiotemporal architecture of immune cells and cancer-associated fibroblasts in high-grade serous ovarian carcinoma

Alexander M. Xu & Sandra Orsulic et al. · 2024-04-17

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.

Funding

BLRD VA

I01 BX004974

BLRD VA

I01 BX006020

NCI NIH HHS

R01 CA208753

NCATS NIH HHS

UL1 TR001881