TY  - JOUR
A1  - Nickl, Vera
A1  - Eck, Juliana
A1  - Goedert, Nicolas
A1  - Hübner, Julian
A1  - Nerreter, Thomas
A1  - Hagemann, Carsten
A1  - Ernestus, Ralf-Ingo
A1  - Schulz, Tim
A1  - Nickl, Robert Carl
A1  - Keßler, Almuth Friederike
A1  - Löhr, Mario
A1  - Rosenwald, Andreas
A1  - Breun, Maria
A1  - Monoranu, Camelia Maria
T1  - Characterization and optimization of the tumor microenvironment in patient-derived organotypic slices and organoid models of glioblastoma
JF  - Cancers
N2  - 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 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.
KW  - glioblastoma
KW  - organoids
KW  - slice culture
KW  - tumormicroenvironment
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319249
SN  - 2072-6694
VL  - 15
IS  - 10
ER  -