Immune Evasion Mechanisms in Early Stage-I High-Grade Serous Ovarian Carcinoma: Insights into Regulatory T-Cell Dynamics

The mechanisms driving immune evasion in early stage-I high-grade serous ovarian carcinoma (HGSOC) remain poorly understood. To investigate this, we performed single-cell RNA-sequencing analysis. Our findings revealed a highly immunosuppressive HGSOC microenvironment, characterized by the infiltration of regulatory T cells (Tregs). Trajectory analysis uncovered differentiation pathways of naïve Tregs, which either underwent activation and proliferation or experienced transcriptional instability. The predicted network of Treg-cell interactions, including those with tumor cells, facilitate Treg mobility, maturation, and reinforced their immunosuppressive function and persistence. Treg-mediated interactions predict the inhibition of CD8+ T cells and antigen-presenting cells, supporting tumor immune escape. Additionally, we observed that more immunogenic tumor conditions, marked by IFN? production, likely contributed to Treg destabilization. Our findings underscore the pivotal role of Tregs in early immune evasion and provide valuable insights into potential therapeutic strategies targeting Treg cell activity and differentiation fate. Overall design: scRNA-seq analysis was conducted on tumor lesions and PBMCs from two incidentally diagnosed stage- I HGSOC patients who underwent ovarian resection without prior chemotherapy treatment. scRNA-seq analysis of tumor lesions was conducted on FACS-sorted tumor-associated CD45+ immune cells and their CD45- tumor counterpart.