Multimodal treatment adding immunotherapy and photodynamic treatment (PDT) to
standard therapy might improve the devastating therapeutic outcome of glioblastoma multiforme
patients. As a first step, we provide investigations to optimize dendritic cell (DC) vaccination by
using PDT and ionizing radiation (IR) to achieve maximal synergistic effects. In vitro experiments
were conducted on murine glioblastoma GL261 cells, primary DCs differentiated from bone marrow
and T cells, isolated from the spleen. Induction of cell death, reactive oxygen species, and inhibition
of proliferation by tetrahydroporphyrin-tetratosylat (THPTS)-PDT and IR were confirmed by WST-1,
LDH, ROS, and BrdU assay. Tumor cargo (lysate or cells) for DC load was treated with different
combinations of THPTS-PDT, freeze/thaw cycles, and IR and immunogenicity analyzed by induction
of T-cell activation. Cellular markers (CD11c, 83, 86, 40, 44, 69, 3, 4, 8, PD-L1) were quantified by
flow cytometry. Cytotoxic T-cell response was evaluated by calcein AM assay. Immunogenicity of
THPTS-PDT-treated GL261 cells lysate was superior to IR-treated lysate, or treated whole cells proven
by increased DC phagocytosis, T-cell adhesion, proliferation, cytolytic activity, and cytokine release.
These data strongly support the application of PDT together with IR for optimal immunogenic cell
death induction in tumor cell lysate used to pulse DC vaccines.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:87051 |
| Date | 08 September 2023 |
| Creators | Rothe, Friederike, Patties, Ina, Kortmann, Rolf-Dieter, Glasow, Annegret |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 10.3390/molecules27113384 |
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