Authors
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
Published in
Nature communications. Jul 11, 2026. Epub Jul 11, 2026.
Abstract
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.
PMID:
42436127
Bibliographic data and abstract were imported from PubMed on 12 Jul 2026.
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