gms | German Medical Science

66. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Friendship Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

7. - 10. Juni 2015, Karlsruhe

The role of regulatory T-cells, FOXP3 and transforming growth factor beta in gliomas – insights into immunosuppressive mechanisms

Meeting Abstract

  • Stephanie Schipmann - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Münster
  • Erol Akalin - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Münster
  • Nils Warneke - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Münster
  • Juliane Schroeteler - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Münster
  • Michael Schwake - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Münster
  • Walter Stummer - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Münster
  • Georg Brunner - Abteilung für Tumorforschung, Fachklinik Hornheide, Münster
  • Christian Ewelt - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Münster

Deutsche Gesellschaft für Neurochirurgie. 66. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Karlsruhe, 07.-10.06.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. DocDI.03.05

doi: 10.3205/15dgnc109, urn:nbn:de:0183-15dgnc1093

Veröffentlicht: 2. Juni 2015

© 2015 Schipmann et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objective: Not only are regulatory T cells (Tregs) an essential component of the immune system in maintaining immunologic self-tolerance by suppressing expansion of immune cells but they are also involved in the suppression of anti-tumour immune responses. The transcription factor forkhead box P3 (FOXP3) is widely used as a marker for the identification of Tregs. FOXP3 is known as being essential for the functionality of Tregs, serving as a master control gene. It is known that T cell development and tolerance are highly dependent on a regulatory network that is modulated by transforming growth factor-beta (TGF-beta). Belonging to a family of regulatory cytokines that have pleiotropic functions, TGF-beta is secreted as a latent complex and is activated by certain mechanisms. Gaining more knowledge regarding the pathogenesis of gliomas, the tumour microenvironment came to the fore. In this study, patterns of Treg recruitment and TGF-beta expression in the microenvironment of gliomas were characterised.

Method: Tregs present in the tumour microenvironment were detected by double-immunohistochemistry for FOXP3 and the glioma marker, anti-glial fibrillary acidic protein (GFAP). FOXP3 mRNA expression was examined, using quantitative real-time-PCR. Active TGF-beta in tumour tissue was determined using the plasminogen activator inhibitor-I promoter luciferase (PAI/L) assay. Appropriate cell lines were analysed.

Results: Tregs were found in the tumour microenvironment as well as within tumour cell islets, and FOXP3 mRNA expression was increased. Intriguingly, single FOXP3+ cells exhibited morphologic characteristics of glioma cells. Our study showed differences regarding FOXP3 expression between glioma grades indicating that Tregs are more present in high-grade gliomas. Active TGF-beta was expressed by glioblastomas in high concentrations.

Conclusions: Gliomas recruit Tregs into their microenvironment, presumably in order to suppress immunosurveillance, thus avoiding destruction by the immune system. Endogenous FOXP3 expression in glioma cells might present a novel mechanism of immune escape. FOXP3 expression is higher in glioblastomas than in low-grade gliomas, indicating that FOXP3 plays a crucial role in creating an immuosuppressive microenvironment in malignant gliomas. In addition, TGF-beta is assumed to play an important role in the generation of a tumour-supporting microenvironment. These findings suggest FOXP3, TGF-beta and Tregs as possible therapeutic targets in the therapy of gliomas.