Scholarlink

<p>High-grade serous carcinoma tumours present poor survival rates, often associated with immunologically excluded environments driven by hypoxia and extensive extracellular matrix remodelling that disrupt tumour-stromal-immune interactions. Current experimental models fail to fully capture these microenvironmental features, limiting understanding of tumour-immune dynamics and drug development. Here, we present bioengineered patient-derived tumour-immune models to mimic physiologically relevant oxygen levels and extracellular matrix remodelling. Cancer cells are co-cultured with cancer-associated fibroblasts within human plasma-3D matrices or grown on decellularized human ovaries. Immune cells are either included within the 3D constructs to study multi-cellular interactions or challenged to infiltrate the matrices. We demonstrate that intratumoural hypoxia acts as a friend and a foe enhancing the activation and cytotoxicity of CD8 + T cells while inducing stromal/matrix dysregulation associated with impaired immune infiltration. Targeting TGF-β signalling attenuates the hypoxia-driven stromal-mediated immune exclusion. These relevant models may aid the development of targeted therapies to transform immunologically cold tumours into immunogenic to benefit female patients.</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

Patient-derived model capturing hypoxia and extracellular matrix remodelling of immunologically cold high-grade serous tumours

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月11日

查看全文
  • Simona Plesselova,
  • Hailey Axemaker,
  • Kristin Calar,
  • Oduduabasi Isaiah,
  • Jared Wollman,
  • Somshuvra Bhattacharya,
  • Etienne Z. Gnimpieba,
  • Darci M. Fink,
  • Congzhou Wang,
  • Hiruni Sumanasiri,
  • Kristina W. Thiel,
  • Maria Bell,
  • Pilar de la Puente

摘要

High-grade serous carcinoma tumours present poor survival rates, often associated with immunologically excluded environments driven by hypoxia and extensive extracellular matrix remodelling that disrupt tumour-stromal-immune interactions. Current experimental models fail to fully capture these microenvironmental features, limiting understanding of tumour-immune dynamics and drug development. Here, we present bioengineered patient-derived tumour-immune models to mimic physiologically relevant oxygen levels and extracellular matrix remodelling. Cancer cells are co-cultured with cancer-associated fibroblasts within human plasma-3D matrices or grown on decellularized human ovaries. Immune cells are either included within the 3D constructs to study multi-cellular interactions or challenged to infiltrate the matrices. We demonstrate that intratumoural hypoxia acts as a friend and a foe enhancing the activation and cytotoxicity of CD8 + T cells while inducing stromal/matrix dysregulation associated with impaired immune infiltration. Targeting TGF-β signalling attenuates the hypoxia-driven stromal-mediated immune exclusion. These relevant models may aid the development of targeted therapies to transform immunologically cold tumours into immunogenic to benefit female patients.