Fig. 7: Inhibition of EZH2-92aa sensitizes GSCs to NK cell cytotoxicity and synergizes with immune checkpoint blockade. | Nature Communications

Fig. 7: Inhibition of EZH2-92aa sensitizes GSCs to NK cell cytotoxicity and synergizes with immune checkpoint blockade.

From: Circular EZH2-encoded EZH2-92aa mediates immune evasion in glioblastoma via inhibition of surface NKG2D ligands

Fig. 7

a Illustration of the in situ GBM model in immunocompromised mice and treatment with NK cells. b Kaplan–Meier analysis of mice intracranially implanted with MES28 and GSC23 GSCs with stable KD of circEZH2 or control cells and treated with PBS or NK cells (n = 5 per group). Log-rank test. **P < 0.01. MST, median survival time. Scale bar, 1 mm. Sh-circEZH2+NK vs scramble, MES28 P = 0.0023, GSC23 P = 0.0017; sh-circEZH2+NK vs scramble+NK, MES28 P = 0.0026, GSC23 P = 0.0017; sh-circEZH2+NK vs sh-circEZH2, MES28 P = 0.0025, GSC23 P = 0.0025. c Representative H&E-stained brain slices from mice with indicated treatment in (b). Scale bar, 1 mm. d, e Representative histogram (d) and quantification (e) of the expression of the indicated molecules in NK cells isolated from the abovementioned GBM model (n = 8 per group). scr vs sh, MES28, CD107a P = 7.37e−07, GZMB P = 5.92e−04, Perforin P = 1.97e−05, IFN-γ P = 1.17e−06, TNF-α P = 1.36e−05; GSC23, CD107a P = 2.21e−05, GZMB P = 3.96e−04, Perforin P = 1.09e−04, IFN-γ P = 0.0028, TNF-α P = 0.0040. f Illustration of the in situ GBM model in C57BL/6 mice and treatment with NK cells and the anti-PD1 antibody. g Kaplan–Meier analysis of mice intracranially implanted with GL261 cells with stable circEZH2 KD or scrambled control cells and treated with PBS, NK cells or NK cells combined with an anti-PD1 antibody (n = 5 per group). The log-rank test was performed between the indicated groups. MST, median survival time. h Representative images of H&E-stained brain slices from mice with indicated treatment in (g). Scale bar, 1 mm. i Frequencies of NK or CD8+ T cells positive with the indicated molecules isolated from the tumour mass from the abovementioned GL261 model (n = 5 per group). For NK cell panel, scr+NK vs sh+NK, CD107a P = 0.0085, GZMB P = 0.0020, IFN-γ P = 0.0006; sh+NK vs sh+NK + anti-PD1, CD107a P = 0.0102, GZMB P = 0.0007, IFN-γ P = 5.61e−05; for CD8 T cell panel, scr+NK vs scr+NK + anti-PD1, GZMB P = 0.0041, IFN-γ P = 0.0035; sh+NK vs sh+NK + anti-PD1, GZMB P = 0.0224, IFN-γ P = 0.0006. The data are presented as the mean ± SD values. Unpaired two-tailed Student’s t test was used to determine the significance of differences between the indicated groups. ns, nonsignificant, *P < 0.05; **P < 0.01; ***P < 0.001. Source data are provided as a Source data file.

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