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.

High-grade serous tumors are immunologically cold, characterized by limited immune cell infiltration and reduced clinical outcome, primarily due to hypoxia and extensive extracellular matrix remodeling that disrupt tumor-stromal-immune interactions. 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 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.

Multicompartmentalized microvascularized tumor-on-a-chip to study tumor-stroma interactions and drug resistance in ovarian cancer.

Introduction: The majority of ovarian cancer (OC) patients receiving standard of care chemotherapy develop chemoresistance within 5 years. The tumor microenvironment (TME) is a dynamic and influential player in disease progression and therapeutic response. However, there is a lack of models that allow us to elucidate the compartmentalized nature of TME in a controllable, yet physiologically relevant manner and its critical role in modulating drug resistance.

Normal Uterine Fibroblast Are Reprogramed into Ovarian Cancer-Associated Fibroblasts by Ovarian Tumor-derived Conditioned Media.

Cancer-associated fibroblasts (CAFs) are key contributors to ovarian cancer (OC) progression and therapeutic resistance through dysregulation of the extracellular matrix (ECM). CAFs are a heterogenous population derived from different cell types through activation and reprogramming. Current studies rely on uncharacterized heterogenous primary CAFs or normal fibroblasts that fail to recapitulate CAF-like tumor behavior.