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. Author manuscript; available in PMC: 2021 Jul 1.
Published in final edited form as: Clin Cancer Res. 2020 Nov 25;27(1):276–287. doi: 10.1158/1078-0432.CCR-20-2291

Figure 1. Concurrent dexamethasone reduces the survival benefit of anti-PD-1 therapy in GL261-luc2 glioblastoma mouse models in a dose-dependent manner.

Figure 1.

(A) Experimental schema. Anti-PD-1 (αPD1, red arrows) was administered in a dose-intensive schedule, i.e. IP beginning on day 6 (500 μg) followed by 7 additional doses (250 μg/dose) at 3-day intervals, with dexamethasone delivered IP daily from days 6–27. (B) Kaplan-Meier survival estimates of anti-PD-1 therapy without dexamethasone (n=42, data derived from 5 experiments, with 8–10 mice each) and anti-PD-1 therapy with concurrent dexamethasone at 1 mg/kg (n=34, data derived from 4 experiments, with 8–10 mice each), 2.5 mg/kg (n=16, data derived from 2 experiments, with 8 mice each), or 10 mg/kg (n=34, data derived from 4 experiments, with 8–10 mice each), compared to IgG (n=42, data derived from 5 experiments, with 8–10 mice each) and 10 mg/kg dexamethasone-only (n=8, data derived from a single experiment) controls; with comparison by Cox regression. (C) The corresponding longitudinal bioluminescence imaging, displayed as change from baseline (day 6 after implantation, dotted gray line), for mice treated with anti-PD-1 alone (n=42, baseline BLI median 415,600 ph/sec/cm2/sr, interquartile range [IQR] 201,500–981,050) or anti-PD-1 with concurrent 1 mg/kg (n=34, baseline BLI median 434,700 ph/sec/cm2/sr, IQR 246,975–835,500), 2.5 mg/kg (n=16, baseline BLI median 490,950 ph/sec/cm2/sr, IQR 268,800–1,081,875), or 10 mg/kg dexamethasone (n=34, baseline BLI median 367,300 ph/sec/cm2/sr, IQR 227,400–636,675), as compared to IgG control (n=16, baseline BLI median 463,650 ph/sec/cm2/sr, IQR 286,775–1,059,250) and dexamethasone 10 mg/kg only control (n=8, baseline BLI median 159,550 ph/sec/cm2/sr, IQR 143,725–231,700). Tumor response visualized in red and lack of response in blue. (D) Representative longitudinal MRI findings demonstrating increased tumor growth when low (1 mg/kg) or high (10 mg/kg) doses of dexamethasone were co-administered during PD-1 therapy, compared to anti-PD-1 without dexamethasone. Images are obtained serially from the same mice over time. Dotted red line outlines the tumor on coronal MRI plane.

ns, not significant, p≥0.05; *p<0.05; **p<0.01; ***p<0.001; Dex, dexamethasone; BLI, bioluminescence imaging; OS, overall survival; 95CI, 95% confidence interval; NR, not reached.