Back to Search Start Over

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

Authors :
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
Source :
Cells [Cells] 2023 Jul 14; Vol. 12 (14). Date of Electronic Publication: 2023 Jul 14.
Publication Year :
2023

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.

Details

Language :
English
ISSN :
2073-4409
Volume :
12
Issue :
14
Database :
MEDLINE
Journal :
Cells
Publication Type :
Academic Journal
Accession number :
37508520
Full Text :
https://doi.org/10.3390/cells12141856