Scholarlink

<p>High-grade serous ovarian cancer (HGSOC) is characterized by a complex, immunosuppressive tumor microenvironment (TME) that contributes to poor clinical outcomes and resistance to therapy. To replicate the human TME in vitro, we develop a 3D pentaculture model incorporating five human cell types: malignant HGSOC cells and primary fibroblasts, mesothelial cells, adipocytes, monocytes. Monocytes differentiate into macrophages without exogenous cytokines in the pentacultures. Bulk RNA sequencing and deconvolution with single-cell RNA data from patient biopsies reveal that macrophage clusters within the pentacultures replicate those found in human HGSOC metastases, and proportions of individual clusters vary according to the malignant cell line. The pentacultures enable detailed analysis of malignant cell–macrophage interactions and highlight the influence of malignant cell genomic, transcriptomic and proteomic heterogeneity on the TME. Furthermore, targeting of “do-not-eat-me” signals with anti-CD47 and anti-CD24 monoclonal antibodies demonstrate differential effects on macrophage activity and cancer cell viability, again depending on the individual malignant cell line. Real-time microscopic monitoring of the pentacultures confirms dynamic modulation of macrophage behavior. We conclude that this pentaculture model offers a platform to study malignant cell control of TME elements and in particular their interactions with myeloid cells.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

3D pentaculture model unveils malignant cell-driven macrophage polarization in high-grade serous ovarian cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月25日

查看全文
  • Beatrice Malacrida,
  • Samar Elorbany,
  • Florian Laforêts,
  • Faisal Karim,
  • Rachel C. Bryan-Ravenscroft,
  • Michail Sideris,
  • Joash D. Joy,
  • Panoraia Kotantaki,
  • Sophie L. P. Skingsley,
  • Owen M. Heath,
  • Ranjit Manchanda,
  • Eleni Maniati,
  • Frances R. Balkwill

摘要

High-grade serous ovarian cancer (HGSOC) is characterized by a complex, immunosuppressive tumor microenvironment (TME) that contributes to poor clinical outcomes and resistance to therapy. To replicate the human TME in vitro, we develop a 3D pentaculture model incorporating five human cell types: malignant HGSOC cells and primary fibroblasts, mesothelial cells, adipocytes, monocytes. Monocytes differentiate into macrophages without exogenous cytokines in the pentacultures. Bulk RNA sequencing and deconvolution with single-cell RNA data from patient biopsies reveal that macrophage clusters within the pentacultures replicate those found in human HGSOC metastases, and proportions of individual clusters vary according to the malignant cell line. The pentacultures enable detailed analysis of malignant cell–macrophage interactions and highlight the influence of malignant cell genomic, transcriptomic and proteomic heterogeneity on the TME. Furthermore, targeting of “do-not-eat-me” signals with anti-CD47 and anti-CD24 monoclonal antibodies demonstrate differential effects on macrophage activity and cancer cell viability, again depending on the individual malignant cell line. Real-time microscopic monitoring of the pentacultures confirms dynamic modulation of macrophage behavior. We conclude that this pentaculture model offers a platform to study malignant cell control of TME elements and in particular their interactions with myeloid cells.