Journal article
Patient-derived model capturing hypoxia and extracellular matrix remodelling of immunologically cold high-grade serous tumours
Nature communications
07/11/2026
DOI: 10.1038/s41467-026-75262-8
PMID: 42436127
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.
Details
- Title: Subtitle
- Patient-derived model capturing hypoxia and extracellular matrix remodelling of immunologically cold high-grade serous tumours
- Creators
- Simona Plesselova - Sanford ResearchHailey Axemaker - Sanford ResearchKristin Calar - Sanford ResearchOduduabasi Isaiah - Sanford ResearchJared Wollman - Sanford ResearchSomshuvra Bhattacharya - Sanford ResearchEtienne Z Gnimpieba - University of South DakotaDarci M Fink - South Dakota State UniversityCongzhou Wang - South Dakota School of Mines and TechnologyHiruni Sumanasiri - University of IowaKristina W Thiel - University of IowaMaria Bell - Sanford HealthPilar de la Puente - Sanford Health
- Resource Type
- Journal article
- Publication Details
- Nature communications
- DOI
- 10.1038/s41467-026-75262-8
- PMID
- 42436127
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Grant note
- P30CA086862 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R21CA259158 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) RSG-23-1149466-01-CDP / American Cancer Society (American Cancer Society, Inc.) P30GM145398 / U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R37CA291976 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA220729P1 / U.S. Department of Defense (United States Department of Defense) P01CA278375 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P30GM154633 / U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) K22CA263783 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
- Language
- English
- Electronic publication date
- 07/11/2026
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9985183138102771
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