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

Intratumoral heterogeneity of tumour associated macrophages in glioblastoma multiforme

Intratumorale Heterogenität Tumor-assoziierter Makrophagen im Glioblastoma multiforme

Meeting Abstract

  • presenting/speaker Mikael Ispirjan - University Medicine Greifswald, Department of Neurosurgery, Greifswald, Deutschland
  • Sander Bekeschus - ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Greifswald, Deutschland
  • Eric Freund - ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Greifswald, Deutschland
  • Frederik Kinnen - University Medicine Greifswald, Department of Neurosurgery, Greifswald, Deutschland
  • Fabian Wilken - University Medicine Greifswald, Department of Neurosurgery, Greifswald, Deutschland
  • Jörg Baldauf - University Medicine Greifswald, Department of Neurosurgery, Greifswald, Deutschland
  • Steffen K. Fleck - University Medicine Greifswald, Department of Neurosurgery, Greifswald, Deutschland
  • Henry W. S. Schroeder - University Medicine Greifswald, Department of Neurosurgery, Greifswald, Deutschland
  • Sascha Marx - University Medicine Greifswald, Department of Neurosurgery, Greifswald, 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. DocP136

doi: 10.3205/21dgnc424, urn:nbn:de:0183-21dgnc4249

Published: June 4, 2021

© 2021 Ispirjan 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: Previous work of our group did assess the PSGL-1 expression on tumour associated macrophages (TAM) by FACS and Immunohistochemistry (IHC). The FACS and IHC results did not correlate with each other, but we noticed that the samples for both methods came from distinct regions in the tumour (sample for pathology and sample for research). The present study aimed to investigate the intratumoral heterogeneity of TAM in GBM with a special focus on PSGL-1 expression.

Methods: Tumour samples of n=11 GBM patients at initial diagnosis were gathered under neuronavigational guidance from up to 6 different defined regions per tumour of the contrast-enhancing tumour margin. Samples were snap-frozen immediately. Overall 12 antigens were investigated with their immunofluorescence staining utilizing the Operetta CLS high content imager followed by algorithm-driven quantification with the Harmony 4.9 analysis software. Overall expression intensity (Foldchange (FC): MFI to MFI of the negative control) was quantified. Also, the heterogeneity of expression (Score = 0 − (1/(x<1)) × 100) in between different regions of one tumour was quantified.

Results: As expected, GFAP as tumour cell marker showed up with the highest expression level across all patients and sample locations (mean FC 6.9, range from 2.1 to 19.9). A medium expression level (mean FC from 2 to 3.1) was shown for CCR7, CD204, Arg1, iNOS, CD163, CD206 and CSFR1. MHCII, CD16, CD68 and PSGL1 (mean FC = 1.2 to 1.5) were among the low abundant antigens. Interestingly, those low abundant antigens showed up with the highest score in the assessment of the intra-tumoral heterogeneity (Score 7.5 to 10). The lowest intra-tumoral heterogeneity has been seen in GFAP expression (Score 5.5).

Conclusion: The present study reveals a tremendous intratumoral heterogeneity of common surface expression marker of TAM in GBM. Especially low abundant antigens as PSGL-1 have a high intra-tumoral heterogeneity. That shows that immunological studies using one sample per tumour are rather limited in their significance.