Characterization and optimization of the tumor microenvironment in patient-derived organotypic slices and organoid models of glioblastoma
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-319249
- While glioblastoma (GBM) is still challenging to treat, novel immunotherapeutic approaches have shown promising effects in preclinical settings. However, their clinical breakthrough is hampered by complex interactions of GBM with the tumor microenvironment (TME). Here, we present an analysis of TME composition in a patient-derived organoid model (PDO) as well as in organotypic slice cultures (OSC). To obtain a more realistic model for immunotherapeutic testing, we introduce an enhanced PDO model. We manufactured PDOs and OSCs from fresh tissueWhile glioblastoma (GBM) is still challenging to treat, novel immunotherapeutic approaches have shown promising effects in preclinical settings. However, their clinical breakthrough is hampered by complex interactions of GBM with the tumor microenvironment (TME). Here, we present an analysis of TME composition in a patient-derived organoid model (PDO) as well as in organotypic slice cultures (OSC). To obtain a more realistic model for immunotherapeutic testing, we introduce an enhanced PDO model. We manufactured PDOs and OSCs from fresh tissue of GBM patients and analyzed the TME. Enhanced PDOs (ePDOs) were obtained via co-culture with PBMCs (peripheral blood mononuclear cells) and compared to normal PDOs (nPDOs) and PT (primary tissue). At first, we showed that TME was not sustained in PDOs after a short time of culture. In contrast, TME was largely maintained in OSCs. Unfortunately, OSCs can only be cultured for up to 9 days. Thus, we enhanced the TME in PDOs by co-culturing PDOs and PBMCs from healthy donors. These cellular TME patterns could be preserved until day 21. The ePDO approach could mirror the interaction of GBM, TME and immunotherapeutic agents and may consequently represent a realistic model for individual immunotherapeutic drug testing in the future.…
Autor(en): | Vera Nickl, Juliana Eck, Nicolas Goedert, Julian Hübner, Thomas Nerreter, Carsten Hagemann, Ralf-Ingo Ernestus, Tim Schulz, Robert Carl Nickl, Almuth Friederike Keßler, Mario Löhr, Andreas Rosenwald, Maria Breun, Camelia Maria Monoranu |
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URN: | urn:nbn:de:bvb:20-opus-319249 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Neurochirurgische Klinik und Poliklinik |
Medizinische Fakultät / Pathologisches Institut | |
Medizinische Fakultät / Medizinische Klinik und Poliklinik II | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Cancers |
ISSN: | 2072-6694 |
Erscheinungsjahr: | 2023 |
Band / Jahrgang: | 15 |
Heft / Ausgabe: | 10 |
Aufsatznummer: | 2698 |
Originalveröffentlichung / Quelle: | Cancers (2023) 15:10, 2698. https://doi.org/10.3390/cancers15102698 |
DOI: | https://doi.org/10.3390/cancers15102698 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | glioblastoma; organoids; slice culture; tumormicroenvironment |
Datum der Freischaltung: | 18.01.2024 |
Datum der Erstveröffentlichung: | 10.05.2023 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |