Schuster C, Frey B, Fietkau R, Corradini S, Gaipl U, Derer A (2026)
Publication Type: Journal article
Publication year: 2026
Book Volume: 57
Article Number: 101102
DOI: 10.1016/j.ctro.2025.101102
Background and purpose: Glioblastoma is the most aggressive malignant brain tumor with an overall poor prognosis despite advanced chemoradiation approaches. Immunotherapeutic strategies have not been beneficial to date. Even being present only at low level in the brain, dendritic cells (DCs) have the potential to promote anti-tumor immune responses. In this study we aimed to gain insight into the interactions between glioblastoma tumor cells, DCs and T cells to understand the molecular and cellular mechanisms driving immune alterations in glioblastoma during standard treatments for optimizing immune therapies in the future. Material and methods: Impact of the conventional chemoradiation (RCT) treatment scheme of glioblastoma cells on conventional DCs type 1 and 2 (cDC) was tested in a syngeneic murine cell culture setting. GL261-luc2 glioblastoma cells were treated and subsequently co-cultured with cDC1-like and cDC2-like cells. Their immunological status was determined as follows: Expression of activation and immune checkpoint markers was quantified via flow cytometry. Cytokine and chemokine secretion was measured by bead-based immunoassays. Mixed lymphocyte reactions with either CD4+ or CD8+ T cells were performed to determine the potential of cDCs in stimulating T cell proliferation. Results: The cellular contact of cDC1-like cells with RCT-treated glioblastoma cells shifted their immune phenotype to a more activated one, whereas the activation of cDC2-like cells was limited. Furthermore, the extracellular profile of inflammatory and immunoregulatory cytokines and chemokines was highly dependent on the tumor cell treatment scheme in co-culture with cDC1-like cells, with the most pronounced effect after RCT. These modifications in the activation status of cDC1- and cDC2-like cells after tumor cell contact subsequently resulted in significantly enhanced CD8+ and CD4+ T cell proliferation. Conclusion: Current glioblastoma cell treatment impacts on the subsequent activation of cDCs and T cells and should serve as basis for improving immunotherapeutic strategies of brain tumors.
APA:
Schuster, C., Frey, B., Fietkau, R., Corradini, S., Gaipl, U., & Derer, A. (2026). Chemoradiation of glioblastoma cells alters expression of activation and immune checkpoint molecules on type 1 and 2 dendritic cells and impacts on subsequent T cell proliferation. Clinical and Translational Radiation Oncology, 57. https://doi.org/10.1016/j.ctro.2025.101102
MLA:
Schuster, Celina, et al. "Chemoradiation of glioblastoma cells alters expression of activation and immune checkpoint molecules on type 1 and 2 dendritic cells and impacts on subsequent T cell proliferation." Clinical and Translational Radiation Oncology 57 (2026).
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