Mimicking physiologically relevant environments in patient-derived tumor-immune models to target immunologically cold high-grade serous tumors

However, current experimental models fail to fully capture oxygen and matrix microenvironmental features, limiting progress in understanding tumor-immune dynamics and developing effective treatments.

Here, we demonstrate that patient-derived tumor-immune models, mimicking physiologically relevant oxygen levels and extracellular matrix remodeling, recapitulate the hypoxia-induced stromal/matrix dysregulation, which associates with impaired immune infiltration, and enable dissecting targeted opportunities via TGF-β signaling. The models incorporate cancer cells co-cultured with cancer-associated fibroblasts within 3D matrices bioengineered using human plasma or grown on decellularized human ovarian extracellular matrices.