Article
Cellular immunity of malignant glioma patients: prerequisites for dendritic cell vaccination immunotherapy
Zelluläre Immunität von Patienten mit Malignen Gliomen: Vorraussetzungen für eine Immuntherapie mit dendritischen Zellen
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Published: | May 4, 2005 |
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Outline
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Objective
Vaccination therapy with dendritic cells (DC) loaded ex-vivo with tumor antigens is a promising immunotherapeutic approach. However, it relies on intact cellular immunity and efficient generation of mature DC, both of which may be impaired in glioma patients, due to previous therapies or systemic effects of the tumor cells. Therefore, immune status and ex-vivo DC generation from malignant glioma patients were studied.
Methods
To compare the immune status frequencies of white blood cell subsets and monocyte-derived, mature dendritic cells after generation in a two-step culture protocol in autologous plasma-supplemented medium or in serum-free medium from glioma patients and controls were analyzed by flow cytometry.
Results
In patients, frequencies of lymphocytes(28.6±1.6% vs 19.0±1.7%), T-cells(28.9±2.2% vs 17.3±2.6%) and B-cells (4.6±0.7% vs 2.4±0.5%) were reduced, whereas the frequencies of neutrophils(60.7±1.9% and 70.7±2.3%) and monocytes (5.4±0.4% and 6.9±0.5%) were significantly increased. There were no differences in white blood cell counts, the frequency of NK-cells as well as in the major T-cell subsets. Responsiveness of T-cells to lectin stimulation was normal. For monocytes, lower frequencies of CD80+ and CD86+ cells but not of CD40+ and HLA-DR+ cells were observed in patients. Ex-vivo DC generation showed only minor differences between patients and controls in CD80 and HLA-DR expression, respectively. Frequencies of CD83+, CD1a+, CD14-, CD40+ and CD86+ cells were comparable.
Conclusions
Only minor defects in the immune status of glioma patients were observed, which will probably not hamper immunotherapy. Mature DC can be generated successfully, particularly under serum-free conditions, from monocytes of glioma patients in normal numbers and with typical immunophenotypes.