gms | German Medical Science

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

Article

Send article

Systemic alterations of the CD4+ T helper cell phenotype in glioma

Systemische Alterationen des CD4+ T-Helfer-Zell Phänotyps in Gliomen

Meeting Abstract

Search Medline for

  • presenting/speaker Malte Mohme - University Medical Center Hamburg-Eppendorf, Department of Neurosurgery, Hamburg, Deutschland
  • Cecile Maire - University Medical Center Hamburg-Eppendorf, Department of Neurosurgery, Hamburg, Deutschland
  • Alessandra Rünger - University Medical Center Hamburg-Eppendorf, Department of Neurosurgery, Hamburg, Deutschland
  • Laura Glau - University Medical Center Hamburg-Eppendorf, Institute of Immunology, Hamburg, Deutschland
  • Eva Tolosa - University Medical Center Hamburg-Eppendorf, Institute of Immunology, Hamburg, Deutschland
  • Manfred Westphal - University Medical Center Hamburg-Eppendorf, Department of Neurosurgery, Hamburg, Deutschland
  • Katrin Lamszus - University Medical Center Hamburg-Eppendorf, Department of Neurosurgery, Hamburg, 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. DocP149

doi: 10.3205/21dgnc434, urn:nbn:de:0183-21dgnc4347

Published: June 4, 2021

© 2021 Mohme 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

Text

Objective: Cancer is a systemic disease. Due to the exceedingly rare occurrence of metastasis of cerebral glioma, systemic alterations have, however, not been considered to play a major role in disease progression of glioma. CD4+ T helper (TH) cells orchestrate the adaptive immune response in an antigen-specific, cytokine mediated manner. The aim of our study was to investigate how far cerebral glioma impacts the systemic CD4+ immune repertoire.

Methods: We performed a multi-color flow cytometry analysis of the peripheral blood CD4+ TH cell phenotype and cytokine production in 100 patients with IDHwt, 30 IDHmut and 16 IDHmut 1p19q co-deleted gliomas in comparison with age-matched healthy donors (HD). Data was analyzed using a Fortessa LSR and Diva software. Multiparameter analyses were performed using UMAP analyses and SpadeVizR trees. The study was approved by the local ethics committee (PV4904).

Results: We found a significant skewing of the peripheral immunophenotype in IDHwt glioma patients, showing a TH1 expansion and reduced numbers of T follicular helper cells (TFH), TH1* and mucosa associated invariant T (MAIT) cells (p<0.001), while TH2 and TH17 percentages remained stable compared to IDHmut and HD. Interestingly, although TH1 cells were dominant in IDHwt patients (p<0.01), intracellular cytokine staining showed a distinct reduction of IFNg and TNFa production after in vitro stimulation, while IL-4 was significantly increased compared to HD (p<0.05). No alterations between all groups were observed in IL-2, IL-10 or IL-17 production. Profiling of metabolic surface markers further revealed increased expression of GLUT1 on CD4+ T cells in IDHwt patients, indicating an activated CD4+ repertoire compared to HD.

Conclusion: Taken together, our results show a CD4+ TH cell type specific skewing of the peripheral immune repertoire in patients with IDHwt gliomas. Our data highlights the importance of considering malignant glioma as a disease with profound systemic effects fundamentally altering the immune repertoire in affected patients.