Fig. 6

TAMs are the predominant source of GPNMB in resection tissue from GBM patients. A RT-qPCR of GPNMB expression in CD11b+ and CD11b− cells separated from 9 patients with GBMs. Statistical analysis was performed using paired t-test. B Representative staining of patient-derived GBM and non-tumor slices stained for GPNMB (left), IBA1 (middle) and merge with DAPI (right; GPNMB = red, IBA1 = green, DAPI, blue). The image to the right shows a magnified view in the tumor slice. Scale bars, including the magnification, represent 20 µm. C Summary of the percentage of IBA1+/GPNMB+ cells of the samples from GBM (n = 9) and non-tumor (n = 3). Statistical analysis was performed using unpaired t-test. Error bars represent SD. D Pearson correlation of tumor-associated macrophage/microglia markers (y-axis) with GPNMB (x-axis). Top: CD204 (r = 0.84; p ≤ 0.0001), OPN (r = 0.81; p ≤ 0.0001) and CD68 (r = 0.79; p ≤ 0.0001). Middle: PTPRC/CD45 (r = 0.70; p ≤ 0.0001), CD163 (r = 0.70; p ≤ 0.0001) and CD204 (r = 0.59; p ≤ 0.0001). Bottom: HEXB (r = 0.64; p ≤ 0.0001), TMEM119 (r = 0.37; p ≤ 0.0001) and P2RY12 (r = 0.31; p ≤ 0.0001). Data derived from all primary GBM samples of the CGGA data set (n = 225). E GPNMB gene expression of non-immune cell population (CD45−), microglia (MG), macrophages (MPH) and neutrophils in human glioma with IDH wildtype (IDHwt), IDH mutant (IDHmut) and brain metastasis (BrM) using the Brain Tumor Immune Micro Environment dataset [18]. Unlabeled statistical analysis were performed in comparison to the non-immune cell population with 2way ANOVA and Tukey's multiple comparisons test. Error bars represent min to max. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. F The Rho value of correlation between uncommitted (M0, left), pro-inflammatory (M1, middle) and anti-inflammatory (M2, right) macrophage infiltration level (based on TIMER algorithm) and GPNMB gene expression