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

Tumor volume of glioblastoma correlates inverse with immunoglobulin-repertoires of tumor-associated macrophages

Meeting Abstract

  • Svenja Busch - Institut für klinische Chemie, Universitätsmedizin Mannheim, Mannheim, Deutschland
  • Tina Fuchs - Institut für klinische Chemie, Universitätsmedizin Mannheim, Mannheim, Deutschland
  • Amr Abdulazim - Neurochirurgische Klinik, Universitätsmedizin Mannheim, Mannheim, Deutschland
  • Daniel Hänggi - Neurochirurgische Klinik, Universitätsmedizin Mannheim, Mannheim, Deutschland
  • Michael Neumaier - Institut für klinische Chemie, Universitätsmedizin Mannheim, Mannheim, Deutschland
  • Marcel Seiz-Rosenhagen - Neurochirurgische Klinik, Universitätsmedizin Mannheim, Mannheim, 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.28.05

doi: 10.3205/17dgnc562, urn:nbn:de:0183-17dgnc5625

Published: June 9, 2017

© 2017 Busch 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: We have found that tumor-associated macrophages and blood monocytes obtained from glioblastoma patients are capable to recombine immunoglobulin genes and to express antibodies of different classes (IgM, IgG, IgK, IgL). The immunoglobulin-repertoires vary between patients and show a reduced complexity in the tumor as compared to the peripheral blood. The aim of the study was to examine the variations between the single repertoires.

Methods: Tumor-associated macrophages and monocytes were isolated from tumor tissue and peripheral blood of glioblastoma patients (n=15). They were purified to homogeneity using sequential affinity purifications (MACS-beads). Absence of lymphocytic cells was verified by high-sensitivity PCR assays. The expression of Igs in the cell preparations were investigated using repertoire-PCRs followed by TOPO-cloning and Sanger sequencing. Analyses of CDR3 regions and the V-, D- and J-chain usage of the Igs were performed using IgBLAST and VBASE2. The complexity of the Ig-repertoires was correlated to the individual tumor size of the patient as assessed by 3D volumetry in preoperative MR images.

Results: The evaluation of the Ig-repertoires from the myeloid cells showed significantly reduced complexity in the tumors when compared to the peripheral blood samples of the individual patients. Moreover, these repertoires are generally more restricted than the corresponding B-cell repertoires. Interestingly, the complexity of the myeloid antibody repertoires shows an inverse correlation to the individual tumor volumes in patients suffering from glioblastoma. Specifically, decrease of complexity in the repertoires can be found the larger the tumor is in size. This phenomenon can be detected in the tumor and in the blood for the heavy as well as for the light chains.

Conclusion: The Ig-repertoires in glioblastoma patients vary significantly between TAMs and circulating monocytes suggesting specific homing and/or immunosuppressive functions exerted by the tumor. This is further corroborated by the observation of a strong inverse correlation between the individual tumor size of the patient and the complexity of the Ig-repertoires expressed by tumor-associated macrophages and monocytes. Further studies are needed to investigate potential functions of the myeloid antibody repertoires and their dynamics during the course of the disease.