Artikel
Immune status of patients with malignant gliomas: Prerequisites for dendritic cell-based immunotherapy
Immunstatus von Patienten mit malignen Gliomen: Vorraussetzungen für eine Immuntherapie mit dendritischen Zellen
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Autoren
Veröffentlicht: | 23. April 2004 |
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Gliederung
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Objective
Vaccination therapy with dendritic cells (DC) loaded ex-vivo with tumor antigens is a promising immunotherapeutic approach, which may allow killing tumor cells specifically without damaging normal tissues. However, DC-based immunotherapy relies on ex-vivo generation of DC as well as on intact cellular immunity, both of which may be impaired in glioma patients, due to previous therapies or systemic effects of the tumor cells.
Methods
The immune status and ex-vivo DC generation were compared for patients with malignant glioma (14 x GBM IV, 4 x AA III) and controls (n=23) by flow cytometry.
Results
In patients, the incidence of lymphocytes (20.7±1.7% vs. 28.6±1.6%) and CD3+ T-cells (21.9±2.9% vs. 28.9±2.2%) were significantly reduced, whereas the incidence of neutrophils (68.0±2.2% vs. 60.7±1.9%) was significantly increased. There were no significant differences in white blood cell counts or incidences of CD14+ monocytes, CD19+ B-cells and CD56+ T- and NK-cells. Immunophenotypic characterization of T-cells revealed a significantly decreased incidence of CD25+ T-cells in patients (4.9±0.6% vs. 7.8±1.0%). There were no significant differences in the incidences of CD4+, CD8+, CD28+, CD45RA+, CD45R0+, CD152+, CD154+ and HLA-DR+ T-cells. Functionally, there was a slightly better mitogen-responsiveness of T-cells from patients as compared to controls. In the monocyte compartment, the only phenotypic difference observed was a lower incidence of CD80+ cells in patients (38.5±10.6% vs. 72.3±5.5%). There were no differences in CD40, CD86 and HLA-DR expression. DC differentiation of monocytes revealed more homogenous generation of mature CD83+/CD14- DC for patients compared to controls. Residual CD14 expression was lower and expression of CD83 as well as CD80 and CD25 was higher for patients, whereas there was no difference in CD1a, CD40, CD86 and HLA-DR expression, in DC yield and viability.
Conclusions
Only minor differences between glioma patients and controls were observed, which will probably not affect DC-based immunotherapy.