Abstract
INTRODUCTION
Inflammatory cells are key components of the tumor microenvironment, and cytokines could create a favorable microenvironment to support tumorigenesis. Several studies have reported that IL-6 levels in glioma tissues are associated with the prognosis of patients with glioma; however, IL-6 levels in cerebrospinal fluid (CSF) of glioma patients has not been sufficiently studied yet.
METHODS
The patients with gliomas were treated at the Department of Neurosurgery, University of Kobe, between January 2007 and December 2016. CSF was withdrawn from the patients via lumbar puncture, and IL-6 concentration was measured by ELISA. after obtaining informed consent when not contraindicated. Infiltration of tumor-associated macrophages (TAMs) were analyzed by CD163 staining.
RESULTS
Seventy-six patients with gliomas were analyzed in this study. The median follow-up period was 25 months. At the end of the follow-up period, 22 patients were alive, and 53 patients were dead. In the pre-treatment CSF examination, mean concentration of IL-6 was 26.3 ± 88.5 pg/ml. In glioblastoma alone, the mean value of CSF IL-6 was 35.6 ± 102.5 pg/ml, which was significantly higher than that of other grades of gliomas. The concentration of CSF IL-6 was correlated with the concentration of CSF LDH. IL-6 protein was expressed in the area where TAMs were predominantly existed. In double immunostaining examination, IL-6 protein was expressed in TAMs, and the concentration of CSF IL-6 was statistically correlated with the percentage of TAMs infiltration in the tumor (p=0.014). In multivariate analysis, high levels of CSF IL-6 were significantly associated with shorter overall survival (HR=1.007, 95% CI: 1.002~-.012, p=0.0049)
CONCLUSIONS
These results indicated that the concentration of CSF IL-6 may reflect the microenvironment of the tumor and may be a useful prognostic biomarker for glioma patients.