A patient-specific lung tumoroid platform recapitulates tumor microenvironments for modeling in vitro therapeutic responses and immune-stromal interactions

Here, we developed patient-specific lung cancer tumoroid (LCT) models integrating TME by reassembling lung cancer organoids (LCOs), cancer-associated fibroblasts (CAFs) and immune cells, which isolated and expanded from tumor tissues by using a modular Transwell-based culture system.

LCTs retained major TME components and spatial organization of the primary tumor. The system supported high-fidelity pharmacologic screening, immune profiling, and mechanistic analysis of treatment-induced TME remodeling. Using LCTs, we observed tumor-intrinsic variation in immune engagement, CAF-mediated modulation, and an uncoupling between metabolic activation and immune stimulation.