TY  - JOUR
AU  - Mansouri, Siavash
AU  - Karger, Annika
AU  - Ruppert, Clemens
AU  - Schneider, Marc A
AU  - Weigert, Andreas
AU  - Nandigama, Rajender
AU  - Aliraj, Blerina
AU  - Strotmann, Lisa
AU  - Cherian, Anoop V
AU  - Pruefer, Diethard
AU  - Dorfmuller, Peter
AU  - Fink, Ludger
AU  - Alkoudmani, Ibrahim
AU  - Gattenlöhner, Stefan
AU  - Eul, Bastian
AU  - Althoff, Andre
AU  - Kleine, Peter
AU  - Winter, Hauke
AU  - Guenther, Andreas
AU  - Ghofrani, Hossein-Ardeschir
AU  - Pullamsetti, Soni S
AU  - Grimminger, Friedrich
AU  - Seeger, Werner
AU  - Savai, Rajkumar
TI  - Living human lung slices for ex vivo modelling of lung cancer.
JO  - JCI insight
VL  - 10
IS  - 17
SN  - 2379-3708
CY  - Ann Arbor, Michigan
PB  - JCI Insight
M1  - DKFZ-2025-01875
SP  - e190703
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Lung Neoplasms: pathology
KW  - Lung Neoplasms: immunology
KW  - Lung Neoplasms: therapy
KW  - Tumor Microenvironment: immunology
KW  - Lung: pathology
KW  - Lung: immunology
KW  - Cell Proliferation
KW  - Cell Line, Tumor
KW  - Macrophages: immunology
KW  - Cell Movement
KW  - Immunology (Other)
KW  - Immunotherapy (Other)
KW  - Lung cancer (Other)
KW  - Oncology (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40728884
DO  - DOI:10.1172/jci.insight.190703
UR  - https://inrepo02.dkfz.de/record/304483
ER  -