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Braun, F.K.* ; Rothhammer-Hampl, T.* ; Lorenz, J.* ; Pohl, S.* ; Menevse, A.N.* ; Vollmann-Zwerenz, A.* ; Bumes, E.* ; Büttner, M. ; Zoubaa, S.* ; Proescholdt, M.* ; Schmidt, N.O.* ; Hau, P.* ; Beckhove, P.* ; Winner, B.* ; Riemenschneider, M.J.*

Scaffold-based (Matrigel™) 3D culture technique of glioblastoma recovers a patient-like immunosuppressive phenotype.

Cells 12:17 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Conventional 2D cultures are commonly used in cancer research though they come with limitations such as the lack of microenvironment or reduced cell heterogeneity. In this study, we investigated in what respect a scaffold-based (Matrigel™) 3D culture technique can ameliorate the limitations of 2D cultures. NGS-based bulk and single-cell sequencing of matched pairs of 2D and 3D models showed an altered transcription of key immune regulatory genes in around 36% of 3D models, indicating the reoccurrence of an immune suppressive phenotype. Changes included the presentation of different HLA surface molecules as well as cellular stressors. We also investigated the 3D tumor organoids in a co-culture setting with tumor-infiltrating lymphocytes (TILs). Of note, lymphocyte-mediated cell killing appeared less effective in clearing 3D models than their 2D counterparts. IFN-γ release, as well as live cell staining and proliferation analysis, pointed toward an elevated resistance of 3D models. In conclusion, we found that the scaffold-based (Matrigel™) 3D culture technique affects the transcriptional profile in a subset of GBM models. Thus, these models allow for depicting clinically relevant aspects of tumor-immune interaction, with the potential to explore immunotherapeutic approaches in an easily accessible in vitro system.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Gbm ; Brain Cancer ; Next-generation Sequencing ; Single-cell Rna Sequencing ; Tumor Organoids; Central-nervous-system; Temozolomide; Cells; Microenvironment; Classification; Immunotherapy; Expression; Generation; Subtypes; Therapy
ISSN (print) / ISBN 2073-4409
e-ISSN 2073-4409
Journal Cells
Quellenangaben Volume: 12, Issue: 14, Pages: , Article Number: 17 Supplement: ,
Publisher MDPI
Publishing Place Basel
Non-patent literature Publications
Institute(s) Institute of Computational Biology (ICB)
Grants German Research Foundation (Deutsche Forschungsgemeinschaft, DFG)
Bavarian Research Network on the interaction of human brain cells (ForInter)