# Exploratory Study of Serum IL-22 and CD163+ Macrophages in Glioblastoma Multiforme

## TL;DR

This study explores the role of IL-22 and CD163+ macrophages in glioblastoma, finding that higher IL-22 levels may help diagnose the disease and could indicate a worse prognosis when combined with immune-suppressing cells.

## Contribution

The study identifies IL-22 as a potential diagnostic biomarker and explores its relationship with CD163+ macrophages in glioblastoma.

## Key findings

- GBM patients had significantly higher serum IL-22 levels than healthy controls.
- High IL-22 levels combined with CD163+ macrophage infiltration were linked to shorter survival.
- IL-22 showed moderate diagnostic ability with an AUC of 0.713.

## Abstract

Background and Objectives: Glioblastoma (GBM) is the most aggressive primary tumor of the central nervous system, characterized by high invasiveness and poor prognosis. Inflammation in the tumor microenvironment, including the presence of immunosuppressive M2-macrophages (CD163+), plays a key role in disease progression. The aim of this study was to evaluate serum levels of interleukin-22 (IL-22) in Bulgarian patients with GBM and to analyze its diagnostic role, its relationship with systemic inflammatory markers (NLR), metabolic parameters, and the infiltration of CD163+ cells. Materials and Methods: The study included 41 newly diagnosed patients with GBM and 46 healthy controls. Serum IL-22 levels were measured by ELISA, and the density of CD163+ cells in the tumor tissue was analyzed immunohistochemically. Statistical analysis included Mann–Whitney test, ROC analysis, binary logistic regression, and Kaplan–Meier survival analysis. Results: GBM patients showed significantly higher levels of IL-22 compared to healthy controls (p = 0.001). ROC analysis demonstrated moderate diagnostic ability of IL-22 (AUC = 0.713), with high levels being a potential risk factor for the disease (OR= 2.51). A weak inverse correlation was found between IL-22 and neutrophil-to-lymphocyte ratio (NLR) (p = 0.048). Although IL-22 levels alone did not affect overall survival, patients with high levels of the cytokine and dense stromal infiltration of CD163+ macrophages tended to have shorter overall survival (p = 0.080). Conclusions: IL-22 is a potential diagnostic biomarker, probably reflecting the systemic inflammatory response in GBM. Its prognostic value might be contextually dependent on the tumor microenvironment, as high levels of IL-22 in combination with immunosuppressive macrophages may contribute to a more aggressive course of the disease.