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. Author manuscript; available in PMC: 2022 May 8.
Published in final edited form as: Nat Cancer. 2021 Nov 8;2(11):1136–1151. doi: 10.1038/s43018-021-00267-9

Fig. 5: Depletion of Monocyte-derived TAMs by Clodronate Attenuates the Anti-tumor Effects of MK-8931 Treatment in GBM Xenografts.

Fig. 5:

a,b, Immunofluorescent staining of the microglia marker TMEM119 (in green) and the total TAM marker IBA1 (in red) to detect microglia distribution in GBM xenografts derived from CCF-DI315 GSCs and the adjacent normal brain. Representative immunofluorescent images (a) are shown. Quantifications (b) show the relative fractions of IBA1+/TMEM119+ cells (microglia) in GBM tumors and the adjacent normal brain. Data are shown as means ± SEM. n = 6 tumor samples per group.

c, A schematic illustration showing treatment with clodronate (for depletion of monocyte-derived TAMs) or/and MK-8931 in GBM xenografts derived from CCF-DI315 GSCs. ICI: Intracranial injection; IP: Intraperitoneal injection; IVIS: In Vivo Imaging Systems. Luc: Luciferase.

d, e, Immunofluorescent staining of IBA1 in GBM xenografts derived from CCF-DI315 GSCs and the adjacent normal brain from mice treated with MK-8931 (MK), Clodronate (CLO), MK plus CLO, or the vehicle control. Representative immunofluorescent images (d) of IBA1 staining (in green) are shown. Quantifications (e) show fractions of TAMs (IBA1+ cells) in GBM xenografts with indicated treatment. Data are shown as means ± SEM. n = 6 tumor samples per group. Statistical significance was determined by one-way ANOVA analysis; Ctl vs CLO: p<0.0001; MK vs CLO + MK: p<0.0001.

f, In vivo bioluminescent analysis to monitor intracranial tumor growth of GBM xenografts derived from CCF-DI315 GSCs in mice treated with MK-8931 (MK), Clodronate (CLO), MK plus CLO, or vehicle control. Representative bioluminescent images on the indicated days were shown.

g, Kaplan-Meier survival curves of mice bearing the GSC-derived GBM xenografts treated with MK-8931 (MK), Clodronate (CLO), MK plus CLO, or the vehicle control. n = 5 mice per group. Log-rank analysis was used to assess the significance; p values are indicated on the figure.