Fig. 6: Proinflammatory conditioning of FcRn-silenced IL-12Fc-treated patient-derived GBM explants with intact tumor microenvironment.

A Scheme of an in vitro blood-brain barrier (BBB) model formed by a brain microvascular endothelial cell (BMEC) monolayer in a transwell insert, derived from human induced pluripotent stem cells (iPSCs). B Transport rates of IL-12 variants across a BMEC monolayer in basolateral (brain) to apical (blood) direction. One-way ANOVA with Dunnett’s test to the IL-12Fc NHQ group. Outlier removal based on Grubbs’ test. rIL-12: n = 6, IL-12Fc WT: n = 6, IL-12Fc NHQ: n = 5 experiment repetitions. Whiskers represent the minimum to maximum, middle line represents the mean. C Tumor explants from nine patients with newly diagnosed GBM were trimmed, divided into parallel perfusion bioreactor cultures, and treated with 100 ng/mL IL-12Fc NHQ or control medium for up to 7 days. Supernatants were analyzed using multiplex Proximity Extension Assay (PEA Olink Target 96 IO). D Differentially expressed proteins in supernatants of bioreactors treated with IL-12Fc NHQ compared to control medium. Values with a false discovery rate (FDR) < 0.05 (horizontal red line) are considered significant. The vertical red line marks a fold change of 2. E Barcode plot of the hallmark IFNγ gene set. The vertical bars in the lower part of the plot mark the t-statistic of those genes which are in the gene set against the background expression of the remaining genes in the panel. F Sign plots of normalized protein expression (NPX) at day 7, comparing IL-12Fc NHQ vs control-treated bioreactors. The middle line marks the sample median, the hinges correspond to the first and third quartiles, and the whiskers extend up to a further ±1.5 times the length of said inter-quartile range. All protein level p values are FDR-adjusted and are derived from moderated t-statistics. n = 9 patients/group. Source data are provided as a Source Data file.