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

Menée à partir d'échantillons tumoraux prélevés sur 42 patientes atteintes d'un carcinome séreux ovarien de haut grade, cette étude examine la distribution spatiotemporelle des cellules immunitaires et des fibroblastes associés au cancer puis analyse la contribution de cette distribution à la progression et à la récidive tumorales

Science Advances, Volume 10, Numéro 16, 2024, article en libre accès

Résumé en anglais

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. Spatial protein analysis of ovarian cancer reveals spatial features that predict relapse and may point to possible therapies.