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72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

06.06. - 09.06.2021

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Autologous tumour-lysate loaded dendritic cell vaccination alters the phenotype of tumour-infiltrating lymphocytes in newly diagnosed glioblastoma patients

Autologe tumorlysat-beladene dendritische Zellvakzinierung verändert den Phänotyp von tumor-infiltrierenden Lymphozyten in neudiagnostizierten Glioblastompatienten

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  • presenting/speaker Angeliki Datsi - University Hospital Düsseldorf, ITZ, Düsseldorf, Deutschland
  • Marion Rapp - University Hospital, Department of Neurosurgery, Düsseldorf, Deutschland
  • Jörg Felsberg - University Hospital Düsseldorf, Department of Neuropathology, Düsseldorf, Deutschland
  • Norbert Galldiks - Research Center Jülich, Institute of Neuroscience and Medicine, Jülich, Deutschland
  • Marcel A. Kamp - University Hospital, Department of Neurosurgery, Düsseldorf, Deutschland
  • Daniel Hänggi - University Hospital, Department of Neurosurgery, Düsseldorf, Deutschland
  • Rüdiger V. Sorg - University Hospital Düsseldorf, ITZ, Düsseldorf, Deutschland
  • Michael Sabel - University Hospital, Department of Neurosurgery, Düsseldorf, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie. sine loco [digital], 06.-09.06.2021. Düsseldorf: German Medical Science GMS Publishing House; 2021. DocV074

doi: 10.3205/21dgnc075, urn:nbn:de:0183-21dgnc0752

Published: June 4, 2021

© 2021 Datsi et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: In an on-going phase II clinical trial (GlioVax), patients with newly diagnosed glioblastoma (GBM) are treated with dendritic cell vaccination as add on to the standard radio-/chemotherapy. To assess the impact of the vaccination on tumor immunity, tumor-infiltrating lymphocytes (TILs) in recurrent tumor tissue were analyzed in vaccinated and control patients as well an in primary samples at initial diagnosis.

Methods: Patients with newly diagnosed GBM were treated either with standard radio-/chemotherapy alone or combined with DC vaccination. In the event of MRI-suspected tumor recurrence, patients were subjected to surgery, when medically indicated. Infiltrating lymphocytes in the resected tissue were analyzed using flow-cytometry for T cell subset and activation markers, IFNy-production as well as the expression of immune checkpoint regulators.

Results: After diagnosed tumor recurrence via MRI, 17 patients (10 vaccinated; 7 control) received additional 18FET-PET imaging. In cases of congruent imaging findings, surgery was performed in 10 patients (5 vaccinated; 5 control). In 2 vaccinated patients neuropathological diagnoses revealed treatment-induced changes in the absence of tumor cells and the isolated TILs showed high frequencies of CD69+IFNy-producing CD4+ (17.65%) and CD8+ (35.91%) T cells, indicating an infiltration of reactive T cells, while in the 3 vaccinated and 5 control patients vital tumor cells were detected and a minor T cell infiltration and IFNy-production. The T cells of the 2 pseudo-progressed vaccinated patients showed lower levels of Foxp3 expression but a simultaneous expression of PD-1 and Tim3 together with a T-bethighEomeshigh phenotype.

Conclusion: Here, we report the presence of immunoreactive effector T cells in vaccinated patients. These cells produce high amounts of IFNy, but may be in an exhausted state. These findings might add valuable insights for the understanding of treatment-related changes following multimodal therapy including dendritic cell vaccination.