Scaffold-Based (Matrigel™) 3D Culture Technique of Glioblastoma Recovers a Patient-like Immunosuppressive Phenotype

Braun FK, Rothhammer-Hampl T, Lorenz J, Pohl S, Menevse AN, Vollmann-Zwerenz A, Bumes E, Büttner M, Zoubaa S, Proescholdt M, Schmidt NO, Hau P, Beckhove P, Winner B, Riemenschneider MJ (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Cells MDPI

Book Volume: 12

Article Number: 1856

Journal Issue: 14

DOI: 10.3390/cells12141856

Abstract

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.

Authors with CRIS profile

Beate Winner Professur für Stammzell-Modelle seltener neuraler Erkrankungen

Involved external institutions

Universitätsklinikum Regensburg DE Germany (DE) Leibniz-Institut für Immuntherapie (LIT) / Leibniz Institute for Immunotherapy DE Germany (DE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE)

How to cite

APA:

Braun, F.K., Rothhammer-Hampl, T., Lorenz, J., Pohl, S., Menevse, A.N., Vollmann-Zwerenz, A.,... Riemenschneider, M.J. (2023). Scaffold-Based (Matrigel™) 3D Culture Technique of Glioblastoma Recovers a Patient-like Immunosuppressive Phenotype. Cells, 12(14). https://doi.org/10.3390/cells12141856

MLA:

Braun, Frank K., et al. "Scaffold-Based (Matrigel™) 3D Culture Technique of Glioblastoma Recovers a Patient-like Immunosuppressive Phenotype." Cells 12.14 (2023).

BibTeX: Download