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 abundant infiltration of regulatory T cells (Tregs). Trajectory analysis uncovered differentiation pathways of naïve Tregs, which underwent either activation and proliferation or transcriptional instability. The predicted Treg-cell interaction network, including crosstalk within tumor cells, facilitates Treg mobility and maturation while reinforcing their immunosuppressive function and persistence in the tumor. Moreover, their interactions with immune cells likely inhibit CD8 T cells and antigen-presenting cells, supporting tumor immune escape. Additionally, more immunogenic tumor conditions, marked by IFNγ production, may contribute to Treg destabilization. Our findings underscore the pivotal role of Tregs in early immune evasion of HGSOC and provide insights into potential therapeutic strategies targeting their activity and differentiation fate.
Authors
- Lara Parachini
- Sara Terzoli (ORCID: https://orcid.org/0000-0003-2650-7195)
- Domenico Vitobello (ORCID: https://orcid.org/0000-0001-9184-5698)
- Valentina Cazzetta (ORCID: https://orcid.org/0000-0001-7183-2793)
- Domenico Mavilio (ORCID: https://orcid.org/0000-0001-6147-0952)
- María Estefania Viano (ORCID: https://orcid.org/0000-0001-5107-928X)
- Joanna Mikulak (ORCID: https://orcid.org/0000-0001-8310-9543)
- Barbara Fiamengo (ORCID: https://orcid.org/0000-0001-6351-8964)
- Fabio Grizzi (ORCID: https://orcid.org/0000-0003-0925-742X)
- Rocco Piazza (ORCID: https://orcid.org/0000-0003-4198-9620)
- Maurizio D’Incalci (ORCID: https://orcid.org/0000-0001-8784-1360)
- Sergio Marchini (ORCID: https://orcid.org/0000-0003-1783-7651)
- Gianluca Basso (ORCID: https://orcid.org/0000-0002-8430-4727)
- Paolo Marzano (ORCID: https://orcid.org/0000-0002-5614-4033)
- Laura Mannarino (ORCID: https://orcid.org/0000-0002-0290-4228)
- Mohamed A.A.A. Hegazi (ORCID: https://orcid.org/0000-0001-7810-5011)
- Rosalba Portuesi (ORCID: https://orcid.org/0000-0002-8784-2192)
- Giampaolo Martiniello
Institutions
- Humanitas University (IT)
- University of Milan (IT)
- IRCCS Humanitas Research Hospital (IT)
- University of Milano-Bicocca (IT)
Publication Details
- Journal
- Cell Death and Disease
- Published
- 2025-04-01
- DOI
- https://doi.org/10.1038/s41419-025-07557-5
- Citations
- 9
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 7.18
Funders
- Fondazione Italiana per la Ricerca sul Cancro