Fig. 3. CXCL12 positivity in endothelial cells and glioma cells correlates with PFS in the GLORIA cohort.

a UMAP projection overlayed with CXCL12 mRNA expression in cell types from scRNAseq in human GBM samples (dataset from Abdelfattah et al.³⁵). b Experimental setup of mIF imaging and outline of analysis pipeline. FFPE tissue samples were used for 7-plex mIF imaging; GLORIA cohort (RT + NOX-A12) (n = 10) and SOC cohort (RT; TMZ) (n = 22). All tumor areas were confirmed independently by two neuropathologists. Cell types and CXCL12 positivity were identified as indicated. c Representative images of GBM tissue samples from GLORIA cohort patients (n = 10) showing CXCL12 (yellow) expression in the cell types of interest: CD31⁺ endothelial cells (red); α-SMA⁺ pericytes (blue); CD68⁺ M⏀/microglia (green) and GFAP⁺ glioma cells (magenta). d Frequency of CXCL12⁺ cells per cell type measured in the GLORIA cohort (in blue; different DLs as indicated; n = 10) and in the SOC cohort (in red; n = 22). Unpaired two-tailed Mann–Whitney U test; ns: not significant (p > 0.05). e Spearman’s rank correlation (r_s) calculated between PFS (days) and total CXCL12⁺ cells (%) measured in the GLORIA cohort (left; in blue and with DLs as indicated; n = 10) and in the SOC cohort (right; in red; n = 22). r_s- and p values (two-tailed) are depicted in the corresponding graphs. f Spearman’s rank correlation (r_s) calculated between PFS (days) and CXCL12⁺ endothelial cells (%) out of total endothelial cells (E12), CXCL12⁺ pericytes (%) out of total pericytes (P12), CXCL12⁺ M⏀/Microglia (%) out of total M⏀/microglia (M12) and CXCL12⁺ glioma cells (%) out of total glioma cells (G12) measured in the GLORIA cohort (upper panels; in blue with DLs as indicated; n = 10) and in the SOC cohort (lower panels; in red; n = 22). r_s- and p values (two-tailed) are depicted in the corresponding graphs. Source data are provided as a Source Data file. DL dose level, FFPE formalin-fixed paraffin-embedded, GBM glioblastoma, M⏀ macrophages, mIF multiplexed immunofluorescence, NOX-A12 olaptesed pegol, PFS progression-free survival, RT radiotherapy, scRNAseq single-cell RNA sequencing, SOC standard-of-care, TMZ temozolomide, UMAP uniform manifold approximation, and projection.