Braun, Frank K. and Rothhammer-Hampl, Tanja and Lorenz, Julia and Pohl, Sandra and Menevse, Ayse-Nur and Vollmann-Zwerenz, Arabel and Bumes, Elisabeth and Buettner, Maren and Zoubaa, Saida and Proescholdt, Martin and Schmidt, Nils O. and Hau, Peter and Beckhove, Philipp and Winner, Beate and Riemenschneider, Markus J. (2023) Scaffold-Based (Matrigel™) 3D Culture Technique of Glioblastoma Recovers a Patient-like Immunosuppressive Phenotype. CELLS, 12 (14): 1856. ISSN , 2073-4409
Full text not available from this repository. (Request a copy)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 & TRADE;) 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-& gamma; 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 & TRADE;) 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CENTRAL-NERVOUS-SYSTEM; TEMOZOLOMIDE; CELLS; MICROENVIRONMENT; CLASSIFICATION; IMMUNOTHERAPY; EXPRESSION; GENERATION; SUBTYPES; THERAPY; brain cancer; tumor organoids; GBM; next-generation sequencing; single-cell RNA sequencing |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Neurochirurgie Medicine > Lehrstuhl für Neurologie Medicine > Abteilung für Neuropathologie Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Mar 2024 09:36 |
| Last Modified: | 10 Mar 2024 09:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59518 |
Actions (login required)
 |
View Item |
