Fig. 5

TSPO is expressed in glial tumors by diverse cell populations and CD68-positive macrophages/microglia drive TSPO expression in the tumor infiltration zone. Multiplex OPAL immune fluorescence co-staining (scale bar = 20 μm) of TSPO together with p53 (tumor cell marker), GFAP (astrocytic differentiation marker), CD68/CD11b (microglia/macrophage marker), and CD31 (endothelial cell marker) in a TSPO-PET enriched IDH-wt glioblastoma patient (GBM_11 II) showed that TSPO is expressed in glial tumors by diverse cell populations (a). Spearman correlation of CD68-IHC labelling (%Area) with TSPO-PET enrichment (SUVmax) in solid tumor areas showed almost no association (r = 0.090, *p = 0.015), whereas in infiltration zones a clear association (r = 0.559, ***p < 0.001) was observed (b). Comparison of the mean distribution patterns of CD68-IHC %Area values across different tumor cell content groups showed lowest signals in solid tumors regions, (Tukey multiple comparison test, **p < 0.01) in comparison to tumor-adjacent regions (c). Spearman correlation of TSPO-IHC with CD68-IHC (%Areas) for no tumor (white), some tumor (light grey), infiltration zone (dark grey), and solid tumor (black) revealed strongest TSPO/CD68-IHC association in specimens without histological tumor characteristics (r = 0.686, ***p < 0.001), whereas with increasing content of glial tumor cells association decreases (some tumor: r = 0.414, ***p < 0.001, infiltration zone: r = 0.403, ***p < 0.001, solid tumor: r = 0.027, p = 0.472) (d). Significances are displayed as follows: p > 0.05 = n.s., p < 0.05 = *, p < 0.01 = **, p < 0.001 = ***. CD11b: cluster of differentiation 11b/ integrin alpha M, CD31: cluster of differentiation 31/ platelet and endothelial cell adhesion molecule 1, CD68: cluster of differentiation 68/ macrosialin, GBM: glioblastoma, GFAP: glial fibrillary acidic protein, IDH: isocitrate dehydrogenase, IDH-wt: IDH-wildtype, IHC: immunohistochemistry, p53: tumor protein p53, PET: positron-emission tomography, SUVmax: maximum standardized uptake value