Abstract IA007: Tumor heterogeneity in ovarian clear cell carcinoma

Abstract Ovarian clear cell carcinoma (OCCC) is a gynecologic cancer showing high incidence in East Asia with critical unmet needs for novel therapeutic options. It is a histological subtype with distinct pathological features, molecular profiles, and biological functions. At the bulk transcriptomic level, there are distinct epithelial (EpiCC) and mesenchymal (MesCC) subtypes and immune-related gene expression signatures (irGES) in OCCC tumors. The MesCC subtype or Immune-Hot features are shown to associate with worse clinical outcomes across several cohort studies. During disease progression from early to advanced OCCC, there is a switch from EpiCC to MesCC subtypes and Immune-Cold to Immune-Hot features. Therefore, the landscapes of tumor heterogeneity in early versus advanced OCCC are different. Bulk and spatial profiling revealed that most early OCCC tumors exhibited Immune-Cold features associated with a non-CTLA4 irGES subtype, no tumor infiltrating immune cells (TIIs), and non-immune mimic tumor cells. A subset of early OCCC tumors acquired Immune-Hot features that were associated with a CTLA4 irGES subtype, and TIIs situated adjacent to immune mimic tumor cells. Two translational studies TGOG-4001 and TGOG-4002 have been launched to validate clinical assays for the stratification of Immune-Hot tumors. In advanced OCCC, certain metastatic sites showed high degrees of heterogeneity in spatial transcriptomics with subregions close to the tumor periphery or invasion fronts at the tumor-stromal interface showing inflammatory and EMT-like signals. The primary sites with subregions situated at the tumor core predominantly showed oxidative phosphorylation and low EMT signals. Collectively, OCCC is an ovarian cancer with immense degree of tumor heterogeneity. Comprehensive and in-depth multi-dimensional analysis could facilitate the design of better patient stratification strategies. Citation Format: Ruby Yun-Ju Huang. Tumor heterogeneity in ovarian clear cell carcinoma abstract. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84 (5 Suppl₂): Abstract nr IA007.