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| Status |
Public on Mar 24, 2025 |
| Title |
Immune Evasion Mechanisms in Early Stage-I High-Grade Serous Ovarian Carcinoma: Insights into Regulatory T-Cell Dynamics |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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 IFNγ 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.
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| 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.
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| Contributor(s) |
Mikulak J, Terzoli S, Marzano P, Cazzetta V, D'Incalci M, Marchini S, Mavilio D |
| Citation(s) |
- Mikulak J, Terzoli S, Marzano P, Cazzetta V et al. Immune evasion mechanisms in early-stage I high-grade serous ovarian carcinoma: insights into regulatory T cell dynamics. Cell Death Dis 2025 Apr 1;16(1):229. PMID: 40164596
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| Submission date |
Feb 20, 2025 |
| Last update date |
Apr 10, 2025 |
| Contact name |
Paolo Marzano |
| E-mail(s) |
paolo.marzano@humanitasresearch.it
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| Organization name |
Humanitas Research Hospital
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| Lab |
Unit of Clinical and Experimental Immunology
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| Street address |
Via Alessandro Manzoni 56
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| City |
Rozzano, Milan |
| ZIP/Postal code |
20089 |
| Country |
Italy |
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| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL30173 |
NextSeq 2000 (Homo sapiens) |
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