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Effect of the tumor on macrophage polarization. Cocultures of M0 cells with GB138 (A) and GB83 (B), either adherent cell or spheroid. Expression of CD163 on macrophages was upregulated in cocultures with adherent cells (red column) more than spheroids (gray column). Part of CD163 macrophages expressed FKBP51s (N = 3). Cocultures of M0 cells with GB138 (C) and GB83 (D), either adherent cell or spheroid. Expression of HLA-DR (MFI) on macrophages was upregulated in cocultures with spheroids (gray column). HLA-DR's expression was also registered on tumor cells, particularly spheroids (N = 3). E, Immunoblot of pSTAT6 expression in PBMCs of 5 patients with GBM. Samples 2 and 3 show pSTAT6. Corresponding values of CD163/FKBP51s (top) and PD-L1/FKBP51s or CD206/FKBP51s (bottom) PB-TAMs are also shown. F, Graphic representation of pSTAT6 levels (MFI) in CD163 macrophages from cocultures (N = 5). Coexpression of FKBP51s in CD163 significantly increased pSTAT6 (see Supplementary Fig. S5F and S5G). G, Immunoblot of pSTAT-6 levels in cocultures. Tumor cell–macrophage interaction induced STAT6 activation (N = 3).
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Giordano et al. (2024) studied this question.
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