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Soluble CD95 (Fas/APO-1) in malignant glioma: (no) implications for CD95-based immunotherapy?
J R Streffer1, M Schuster, F Zipp
1Department of Neurology, University of Tübingen, School of Medicine, Germany.
Abstract:
CD95 targeting is a novel approach of immunotherapy for malignant glioma that might be antagonized by the release of soluble CD95 by the tumor cells. An alternatively spliced CD95 mRNA that encodes a secreted CD95 variant has been detected in glioma cell lines in vitro and in human tumors in vivo. Here, we report that the levels of soluble CD95 in the serum of malignant glioma patients do not differ from those of lumbar disk disease patients. Soluble CD95 was detected in the CSF in 2 of 20 malignant glioma patients by ELISA. Bioassay studies indicate that these low levels of soluble CD95 in the CSF of some patients with malignant glioma cells are unlikely to interfere with CD95-based immunotherapy of malignant gliomas in vivo.
Insights
Soluble CD95 levels in serum from malignant glioma patients are similar to controls. Low levels of soluble CD95 in cerebrospinal fluid are unlikely to impede CD95-based immunotherapy for malignant gliomas.
Area of Science:
- Immunotherapy
- Neuro-oncology
- Molecular Biology
Background:
- CD95 targeting represents a promising immunotherapy for malignant glioma.
- Tumor-released soluble CD95 (sCD95) may antagonize CD95-based therapies.
- An alternatively spliced CD95 mRNA encoding a secreted variant has been identified in glioma.
Purpose of the Study:
- To investigate the levels of soluble CD95 in serum and cerebrospinal fluid (CSF) of malignant glioma patients.
- To assess the potential interference of soluble CD95 with CD95-based immunotherapy in vivo.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to quantify soluble CD95 levels in patient serum and CSF.
- Bioassays were conducted to evaluate the functional impact of soluble CD95.
Main Results:
- Serum levels of soluble CD95 in malignant glioma patients were comparable to those in patients with lumbar disk disease.
- Soluble CD95 was detected in the CSF of only 2 out of 20 malignant glioma patients.
- Detected low levels of soluble CD95 in CSF are unlikely to interfere with CD95-based immunotherapy.
Conclusions:
- Soluble CD95 in serum does not appear to be a distinguishing biomarker for malignant glioma.
- The low prevalence and concentration of soluble CD95 in CSF suggest minimal impact on the efficacy of CD95-targeted immunotherapies for malignant gliomas.
