Tumor-associated macrophage related interleukin-6 in cerebrospinal fluid as a prognostic marker for glioblastoma

J Clin Neurosci. 2019 Oct:68:281-289. doi: 10.1016/j.jocn.2019.07.020. Epub 2019 Jul 18.

Abstract

Interleukin-6 (IL-6) is one of the pleiotropic cytokines and has received attention as a critical factor implicated in the invasion and the angiogenesis of various cancers. In glioma, IL-6 is known to be associated with the prognosis; however, the roles of IL-6 in cerebrospinal fluid (CSF) has not been studied sufficiently. We examined the concentration of CSF IL-6 using 75 CSF samples of glioma (54 glioblastomas (GBMs) and 21 other grades of gliomas) and analyzed the association CSF IL-6 with infiltration levels of tumor-associated macrophages (TAMs) and prognosis. The concentration of CSF IL-6 in GBM patients was significantly higher than that in other grades of gliomas. CSF IL-6 levels were associated with the infiltration rate of TAMs in GBMs, and IL-6 levels were increased in the GBM cells co-cultured with TAM-like macrophages. The CSF of GBM patients, which contained high concentration of IL-6, promoted the migration ability of GBM cells, and neutralization antibodies of IL-6 inhibited its migration ability. Finally, in both univariate and multivariate analysis, higher CSF IL-6 levels were associated with poorer prognosis in GBM patients. These results indicated that the concentration of CSF IL-6 is associated with TAMs' infiltration level and may be a useful prognostic biomarker for the GBM patients.

Keywords: Cerebrospinal fluid; Glioblastoma; IL-6; Prognosis; Tumor-associated macrophage.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / cerebrospinal fluid*
  • Biomarkers, Tumor / immunology
  • Brain Neoplasms / cerebrospinal fluid
  • Brain Neoplasms / immunology*
  • Brain Neoplasms / pathology
  • Cell Movement / immunology
  • Female
  • Glioblastoma / cerebrospinal fluid
  • Glioblastoma / immunology*
  • Glioblastoma / pathology
  • Humans
  • Interleukin-6 / cerebrospinal fluid*
  • Macrophages / immunology
  • Macrophages / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Young Adult

Substances

  • Biomarkers, Tumor
  • IL6 protein, human
  • Interleukin-6