Various immune cells infiltrate glioma tissues and secrete inflammatory mediators. This study aimed to identify inflammatory mediators in the CSF that are indicative of the tumor microenvironment (TME) and have prognostic significance in patients with glioma.

This retrospective study included patients newly diagnosed with glioma. CSF concentrations of soluble CD163 (sCD163), a marker of M2 macrophages, were measured using a human ELISA kit and compared with the percentage of CD163-positive area in tumor tissue (tCD163 (%)). In addition, concentrations of 37 inflammatory mediators in CSF were quantified using Bio-Plex Pro™ Human Inflammation Assays. Correlations among these mediators and their associations with clinical outcomes were analyzed.

A total of 125 patients were evaluated for sCD163. Both sCD163 levels and tCD163%) were significantly higher in WHO grade 4 gliomas and showed a positive correlation. Multivariate correlation analysis revealed a clear segregation of CSF inflammatory mediators into sCD163 positive-corelate and sCD163 negative-correlate clusters. sCD163 positive-correlate cluster includes various TNF superfamilies and sTNF receptors, while sCD163 negative-correlate cluster includes interferon-α/β (IFN-α/β) and verous interleukines (ILs). Among patients with IDH-wild glioblastoma, the ratio of sCD163/IFN-α/β was associated with poor prognosis.

Elevated sCD163 levels in CSF were positively associated with various TNFSFs and sTNFRs and inversely associated with type 1 IFNs and various ILs, suggesting a dominant influence of tumor associated M2 macrophages on the TME. The sCD163/type I IFN ratio may serve as a potential prognostic indicator in patients with IDH-wildtype glioblastoma.