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

Sci Adv. 2024 Apr 19;10(16):eadk8805. doi: 10.1126/sciadv.adk8805. Epub 2024 Apr 17.

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.

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Cancer-Associated Fibroblasts* / pathology
  • Female
  • Humans
  • Neoplasm Recurrence, Local
  • Ovarian Neoplasms* / drug therapy
  • Recurrence
  • Tumor Microenvironment

Substances

  • Antineoplastic Agents