Figure 2: SMCs synergize with innate immunostimulants for the treatment of glioblastoma. | Nature Communications

Figure 2: SMCs synergize with innate immunostimulants for the treatment of glioblastoma.

From: Smac mimetics synergize with immune checkpoint inhibitors to promote tumour immunity against glioblastoma

Figure 2

(a) Mice bearing intracranial CT-2A tumours were treated with 75 mg kg−1 LCL161 (SMC, oral) and tumours and surrounding (non-tumorous) brain tissues were harvested at the indicated times for western blotting using the indicated antibodies. n=1 for control and n=2 for SMC-treated mice. (b) TNF-α levels from serum or solubilized brain homogenates was determined by ELISA of mice treated with PBS or 50 μg poly(I:C) i.p. or 5 × 108 PFU of VSVΔ51 i.v. Crosses depict mean, solid horizontal lines depict median, boxes depict 25th to 75th percentile, and whiskers depict min–max range of the values. n=4 for control mice and n=5 for treated mice for each group. Significance was compared with PBS treatment using ANOVA with Dunnett’s multiple comparison test. *P<0.05; ***P<0.001. (c) Mice bearing intracranial tumours were treated at the indicated times with vehicle or 75 mg kg−1 LCL161 (oral), PBS or 50 μg poly(I:C) i.c. or 5 × 108 PFU of VSVΔ51 (i.v.). (d) Representative live MRI images from mice described in (c) were acquired at 40 days post implantation. Scale bar, 2 mm. (e) Alamar blue viability assay of CT-2A cells treated with vehicle or 5 μM LCL161 and 0.01% BSA or 1 μg ml−1 IFN-αB/D. Error bars, mean, s.d. n=4. Representative data from three independent experiments using biological replicates. Statistical significance was compared with vehicle and BSA treatment using ANOVA using Dunnett’s multiple comparison test. Significance is reported if P<0.0001 (*). (f) Mice bearing intracranial CT-2A tumours were treated i.c. at day 7 post-implantation with combinations of vehicle or 75 mg kg−1 LCL161 and 0.01% BSA or 1 μg of IFN-αB/D. (g) Mice bearing 7-days-old intracranial CT-2A tumours were treated with combinations of 75 mg kg−1 LCL161 (oral) and BSA or 1 μg of IFN-αB/D (i.p.). (c,f,g) Data represent the Kaplan–Meier curve depicting mouse survival. Log-rank with Holm–Sidak multiple comparison: **P<0.01; ***P<0.001. Numbers in parentheses represent number of mice per group.

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