gms | German Medical Science

68th Annual Meeting of the German Society of Neurosurgery (DGNC)
7th Joint Meeting with the British Neurosurgical Society (SBNS)

German Society of Neurosurgery (DGNC)

14 - 17 May 2017, Magdeburg

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The potential role of tumor necrosis resulting in an immunosuppressive microenvironment related to major immune suppression and highly detrimental outcome in GBM patients

Meeting Abstract

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  • Andrej Pala - Universitätsklinikum Ulm am Standort Günzburg, Abteilung für Neurochirurgie, Sektion Periphere Nervenchirurgie, Oberelchingen, Deutschland
  • Haouraa Mostafa - Ulm, Deutschland
  • Angelika Scheuerle - Günzburg, Deutschland
  • Michal Hlavac - Günzburg, Deutschland
  • Christian Rainer Wirtz - Bezirkskrankenhaus Günzburg, Neurochirurgische Klinik der Universität Ulm, Günzburg, Deutschland
  • E. Marion Schneider - Universitätsklinik Ulm, Ulm, Deutschland

Deutsche Gesellschaft für Neurochirurgie. Society of British Neurological Surgeons. 68. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 7. Joint Meeting mit der Society of British Neurological Surgeons (SBNS). Magdeburg, 14.-17.05.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. DocMi.28.06

doi: 10.3205/17dgnc563, urn:nbn:de:0183-17dgnc5639

Published: June 9, 2017

© 2017 Pala 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: Current standard therapy of glioblastoma (GBM) patients offers dismal prognosis but individual patients differ in their prognosis. Immune phenotyping may constitute important predictive elements for survival. Generally, tumor-associated immune suppression is one of the major limitations in GBM therapy and T-cell exhaustion may be of highest relevance for immune insufficiency. Tumor necrosis seems to have a relevant influence on tumor microenvironment. We have evaluated the correlation between tumor necrosis volume and immunological characteristics of GBM patients in regard to patients´ outcome.

Methods: Out of 90 analyzed GBM patients, 8 patients with poor and 6 patients with excellent outcome were selected on the basis of overall survival and Karnofsky performance scales (KFS). Tumors were characterized by analyzing their MGMT and IDH-1 mutation status. Volumetric analysis of enhanced T1 MRI images of tumor was assessed using Brainlab iPlan 3.0. Tumor and necrosis volume were evaluated separately. Additionally, necrotic tumor was assessed, questioning the possible contribution of an immunological response in the tumor area. We used antibodies recognizing: CD3, CD8, CD19, CD68, CD163 for flow-cytometry and immune histochemistry to characterize immune activation patterns in peripheral blood, and in the tumor, respectively.

Results: The mean necrotic core volume in patients with unfavourable outcome was 16.098 cm3 (0.428-34.820 cm3). Patients with favourable outcome presented a smaller necrotic tumor core with a mean volume of 2.912 cm3 (0.000 – 6.117 cm3, p=0.025, Mann-Whitney-U Test). Thus the volume/necrosis ratio has shown a significant difference between both cohorts (p=0.007, Mann-Whitney-U test). Remarkably, the high necrotic core ratio was related to a unique deficiency T-cell receptor positive T lymphocytes but preservation of CD19+ B cells. In tumor tissues, however, the infiltration of CD3+/CD8+ T lymphocytes appeared to be similar in dismal patients when compared to patients with a more favourable prognosis.

Conclusion: Patients with unfavourable outcome seem to present with tumors that exhibit large necrotic tumor core. The low tumor/necrosis volume index corresponds with an immunosuppressive environment and inferior survival in GBM patients. Furthermore, significantly decreased amounts of T cell receptor positive lymphocytes implies active immune suppression resulting in faster tumor progress and poor survival.