Living human lung slices for ex vivo modelling of lung cancer
Siavash Mansouri, Annika Karger, Clemens Ruppert, Marc A. Schneider, Andreas Weigert, Rajender Nandigama, Blerina Aliraj, L Strotmann, Anoop V. Cherian, Diethard Pruefer, Peter Dorfmüller, Ludger Fink, Ibrahim Alkoudmani, Stefan Gattenlöhner, Bastian Eul, A. Althoff, Peter Kleine, H. Winter, Andreas Guenther, Hossein-Ardeschir Ghofrani, Soni Savai Pullamsetti, Friedrich Grimminger, Werner Seeger, Rajkumar Savai
Abstract
The tumor microenvironment (TME) markedly affects cancer progression, yet traditional animal models do not fully recapitulate the situation in humans. To address this, we developed tumor-derived precision lung slices (TD-PCLS), an ex vivo platform for studying the lung TME and evaluating therapies. TD-PCLS, viable for 8-10 days, preserve the heterogeneity and metabolic activity of primary tumors, as confirmed by seahorse analysis. Using multispectral FACS and phenocycler multiplex imaging, we spatially profiled TME components and cancer cell functionality. Additionally, TD-PCLS revealed patient-specific responses to chemo- and immunotherapies. To complement TD-PCLS, we established tumor-cell-seeded PCLS (TCS-PCLS) by introducing tumor and immune cells into healthy lung slices. This model highlighted macrophage-tumor interactions as critical for tumor cell proliferation, migration, and immune modulation. Together, these platforms provide a robust tool for lung cancer research, enabling precision medicine and advancing therapeutic discovery.