Artikel
Immune phenotype of glioblastoma patients and properties of established cell lines
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Autoren
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Haouraa Mostafa
- Sektion Experimentelle Anaesthesiologie, Universitätsklinikum Ulm, Germany
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Elvira Dietrich
- Sektion Experimentelle Anaesthesiologie, Universitätsklinikum Ulm, Germany
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Andrej Pala
- Neurochirurgie, Universitätsklinikum Ulm und Bezirkskrankenhaus Günzburg, Germany
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C. Rainer Wirtz
- Neurochirurgie, Universitätsklinikum Ulm und Bezirkskrankenhaus Günzburg, Germany
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E. Marion Schneider
- Sektion Experimentelle Anaesthesiologie, Universitätsklinikum Ulm, Germany
| Veröffentlicht: | 8. Juni 2016 |
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Gliederung
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Objective: Glioblastoma multiforme (GBM) is a lethal brain tumor and largely resistant to current therapies. We here asked whether immune alterations might correlate with defined properties of the GBM tumor in individual patients. We determined the properties of established GBM cell lines. A total of 8 cell lines were investigated for their susceptibility to NK mediated cytolysis. Our main objective was immune modulation of the tumor toward GBM-specific kill.
Method: Patients were extensively characterized before surgery. Immune phenotypes determined by flow cytometry were correlated with survival. Established GBM cell lines were characterized by surface and cytoplasmic antigens. They were tested for their susceptibility against NK mediated apoptosis using allogeneic and autologous non-adherent lymphocytes as well as interleukin- (IL-2), and IL-15 activated effectors. Apoptosis induction was tested by caspase 3/7 and caspase 8 activation.
Results: In a total of 60 GBM patients we found a remarkable downregulation of the T-cell markers CD3 (p<0.0001), CD4 (p<0.0001) and CD8 (p=0.0032) when compared to healthy individuals (n=37). Patients with a relative increase of CD8 positive lymphocytes had a better survival. The same was true for patients with increased relative amounts of activated NK cells expressing CD56+/CD16+ (p=0.0031). All 8 GBM cell lines expressed the NK receptors Trail-DR4, Trail-DR5, CD95 and were positive for MIC-A. Using the caspase 3/7 assays we were able to determine a selective susceptibility to NK-mediated cytolysis in these cell lines.
Conclusions: The currently established screening system implies the relevance of activated NK cells in immune surveillance against GBM. The established cell lines are an excellent source to follow an individual patient’s immunity against its autologous tumor. Moreover, allogeneic NK effector are of potential clinical relevance.
