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FKBP5 splicing in GBM tumors sustains STAT3 activation and is accompanied by systemic tolerogenic immune condition. A, Left, IB of GB138 cell transfected with Flag-FKBP51, Flag-FKBP51s or correspondent EV as control. The spliced FKBP51s, but not the canonical FKBP51, increased pSTAT3 levels (N = 3). Right, IB of GB138 cell transfected with siFKBP51s or a nonsilencing RNA (NS) as control. Compared with control (NS) cells, siFKBP51s treated cells showed impaired levels of pSTAT3 (N = 3). B, Immunoblot of pSTAT3 expression 4 GBMs, samples 2 and 4 show that pSTAT3 corresponded to FKBP51s expression. Linear regression of tumor-FKBP51s with TME-TAMs (C) and PB-TAMs (D). The Pearson correlation coefficient test calculated a positive correlation with the indicated TAMs (see Supplementary Table S2). E, IFNα levels in clusters 1 and 2. F and G, Linear regression of tumor-FKBP51s and IFNα or IL17A. H, Kaplan–Meier curves for OS rates, compared between FKBP51shigh and FKBP51slow patients. The two groups were divided according to the median value of tumor FKBP51s expression. EV = empty vector; IB = immunoblot.
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Giordano et al. (2024) studied this question.
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