Journal Article

DKFZ-2025-01875

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Living human lung slices for ex vivo modelling of lung cancer.

Mansouri, S. ; Karger, A. ; Ruppert, C. ; Schneider, M. A. ; Weigert, A. ; Nandigama, R. ; Aliraj, B. ; Strotmann, L.DKFZ* ; Cherian, A. V. ; Pruefer, D. ; Dorfmuller, P. ; Fink, L. ; Alkoudmani, I. ; Gattenlöhner, S. ; Eul, B. ; Althoff, A. ; Kleine, P. ; Winter, H. ; Guenther, A. ; Ghofrani, H.-A. ; Pullamsetti, S. S. ; Grimminger, F. ; Seeger, W. ; Savai, R.

2025
JCI Insight Ann Arbor, Michigan

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Please use a persistent id in citations: doi:10.1172/jci.insight.190703

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.

Keyword(s): Humans (MeSH) ; Lung Neoplasms: pathology (MeSH) ; Lung Neoplasms: immunology (MeSH) ; Lung Neoplasms: therapy (MeSH) ; Tumor Microenvironment: immunology (MeSH) ; Lung: pathology (MeSH) ; Lung: immunology (MeSH) ; Cell Proliferation (MeSH) ; Cell Line, Tumor (MeSH) ; Macrophages: immunology (MeSH) ; Cell Movement (MeSH) ; Immunology ; Immunotherapy ; Lung cancer ; Oncology

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Contributing Institute(s):

1. B200 Systembiologie der Signaltransduktion (B200)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025

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Database coverage:
; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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