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. 2021 Feb 15;131(4):e139542. doi: 10.1172/JCI139542

Figure 5. Inhibition of IDH1-R132H in combination with SOC and αPD-L1 exhibits enhanced survival of mIDH1 glioma–bearing mice.

Figure 5

(A) Experimental design to assess survival for AGI-5198+SOC+αPD-L1 therapy. (B) Kaplan-Meier survival analysis of C57BL/6 mice treated with saline (n = 5), SOC (n = 5), TMZ (n = 5), αPD-L1+SOC (n = 5), αPD-L1 (n = 5), αPD-L1+TMZ (n = 5), and IR+αPDL (n = 5). (C) Kaplan-Meier survival analysis of C57BL/6 mice treated with saline (n = 5), AGI-5198+TMZ+αPD-L1 (n = 5), AGI-5198+SOC (n = 5), AGI-5198+IR+αPD-L1 (n = 5), and AGI-5198+SOC+αPD-L1 (n = 5). (D) Kaplan-Meier survival plot for rechallenged long-term survivors from (C) AGI-5198+TMZ+αPD-L1 (n = 1), AGI-5198+SOC (n = 2), AGI-5198+IR+αPD-L1 (n = 2), and AGI-5198+SOC+αPD-L1 (n = 3) groups, and control mice (n = 3). Data were analyzed using the log-rank (Mantel-Cox) test. **P < 0.001; ***P < 0.001. (E) Kaplan-Meier analysis of mIDH1 glioma–bearing CD8-KO mice treated with saline (n = 5) or AGI-5198+SOC+αPD-L1 (n = 5). (G) C57BL/6 mice bearing mIDH1 glioma were treated with saline or AGI-5198+SOC+αPD-L1 as detailed in A. At 27 dpi, brains were harvested for immunohistochemistry analysis. Immunofluorescence staining for Ki67 and CC3 was performed on 50 μm vibratome tumor sections. Bar graphs represent total number of positive cells for Ki67 and CC3 in saline or AGI-5198+SOC+αPD-L1 treatment groups. **P < 0.01; ***P < 0.001, unpaired t test. Bars represent mean ± SEM (n = 3 biological replicates). (F) Nissl staining of 50 μm brain sections at 27 dpi from mIDH1 tumor–bearing mice treated with saline and AGI-5198+SOC+αPD-L1. ****P < 0.001; unpaired t test. Bars represent mean ± SEM (n = 3 biological replicates).