Recapitulating physiologically relevant oxygen levels and extracellular matrix remodeling in patient-derived tumor-immune tunable models reveal targeting opportunities for 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 show that patient-derived tumor-immune tunable models mimicking physiologically relevant oxygen levels and extracellular matrix remodeling recapitulate the hypoxia-induced stromal/matrix dysregulation, which causes impaired immune infiltration, and enable dissecting targeted opportunities via TGF-β signaling. The models integrate cancer cells co-cultured with cancer associated fibroblasts and exposed to immune cells as multi-culture or challenged them to infiltrate into a 3D model bioengineered with autologous plasma from the matching patient or onto decellularized human ovaries.