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

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 cu...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2023-07, Vol.12 (14), p.1856
Main Authors: Braun, Frank K, Rothhammer-Hampl, Tanja, Lorenz, Julia, Pohl, Sandra, Menevse, Ayse-Nur, Vollmann-Zwerenz, Arabel, Bumes, Elisabeth, Büttner, Maren, Zoubaa, Saida, Proescholdt, Martin, Schmidt, Nils O, Hau, Peter, Beckhove, Philipp, Winner, Beate, Riemenschneider, Markus J
Format: Article
Language:English
Subjects:
Antigens
Brain cancer
Cell culture
Cellular stress response
Cloning
Flow cytometry
GBM
Glioblastoma
Glioblastoma multiforme
Growth factors
Lymphocytes
Medical prognosis
Methods
Microenvironments
next-generation sequencing
Organoids
Patients
Peptides
Phenotypes
single-cell RNA sequencing
tumor organoids
Tumor-infiltrating lymphocytes
Tumors
γ-Interferon
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Summary: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.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells12141856