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<p>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.</p>

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Immune evasion mechanisms in early-stage I high-grade serous ovarian carcinoma: insights into regulatory T cell dynamics

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月1日

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  • Joanna Mikulak,
  • Sara Terzoli,
  • Paolo Marzano,
  • Valentina Cazzetta,
  • Giampaolo Martiniello,
  • Rocco Piazza,
  • Maria Estefania Viano,
  • Domenico Vitobello,
  • Rosalba Portuesi,
  • Fabio Grizzi,
  • Mohamed A. A. A. Hegazi,
  • Barbara Fiamengo,
  • Gianluca Basso,
  • Lara Parachini,
  • Laura Mannarino,
  • Maurizio D’Incalci,
  • Sergio Marchini,
  • Domenico Mavilio

摘要

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.