196P - Single-cell analysis of stage-I high-grade serous ovarian carcinoma reveals the essential role of regulatory T cells in early tumor establishment

Background

High-grade serous ovarian carcinoma (HGSOC) remains the deadliest gynecologic malignancy, primarily due to its asymptomatic nature in the early-stages and the complex, poorly understood mechanisms driving its progression.

Methods

In this study, we employed single-cell RNA-seq analysis to delve deeper into early-stage of HGSOC, uncovering a previously underappreciated dominant infiltration and heterogeneity of regulatory T (Treg) cells.

Results

Within the HGSOC lesions, we detected CD4 regulatory T cells (Tregs) displaying diverse transcriptomic profiles indicative of their naïve, effector, proliferating, and destabilized states. The presence of Tregs was associated with an immunosuppressive tumor microenvironment, featured by CD4 Th2 cells, exhausted CD8 T cells, lacking cytotoxicity NK cells, and tumor-associated macrophages (TAMs). Cell-to-cell communication analysis predicted Treg-mediated inhibition of immune responses and reciprocal interactions with tumor cells promoting Treg activation. Trajectory analysis revealed two Treg differentiation paths, both leading to immunosuppressive FOXP3^high and FOXP3⁺ Treg profiles. Notably, while the trajectory of FOXP3^high profile converges with proliferating Tregs, the second path of cytotoxic FOXP3⁺ Tregs aligned with FOXP3^- ex-Tregs, distinguished by an anti-tumor CXCL13⁺IFNG⁺ transcriptomic profile.

Conclusions

Therefore, despite the immunosuppressive environment, we identified the counteracting antitumor activity of Tregs, highlighting the potential of manipulating Treg cell fate as for therapeutic strategies.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.