FIGURE 3 from EZH2 Inhibition Promotes Tumor Immunogenicity in Lung Squamous Cell Carcinomas

Murine LSCC organoids share derepression of MHC and pro-T cell cytokines with human models. A, Schematic: Generation of murine tumoroids in air-liquid interface from tumor induced in Lkb1/Pten mice by adenoCre administration, showing H&E stain of tumoroids, scale bar = 100 µm, and brightfield microscopy, scale bar = 200 µm. B, Flow cytometry analysis of two separate murine tumoroid models treated for 11 days with 5 µmol/L EZH2 inhibition with 20 ng/mL IFNγ added on day 9 stained for cell surface expression of NGFR, PD-L1, H2Kd,Dd, and I-A/I-E, n = 5 individual experiments except mouse 2 I-A/I-E and PD-L1; n = 4 individual experiments; *, P < 0.031; **, P < 0.006; ***, P = 0.0002; ****, P < 0.0001 by one-way ANOVA with multiples comparisons and Holm-Šídák post hoc test. C, Heat maps of log2 fold change in expression level from patient-derived and murine tumoroids treated for 11 days with 5 µmol/L EZH2 inhibition with 20 ng/mL IFNγ added in on day 9, G = GSK126, E = EPZ6438, I = IFNγ, I+G = IFNγ+GSK126, and I+E = IFNγ+EPZ6438. For each map, the first columns are sample 1, the second columns are sample 2. Expression relative to vehicle control (left) and relative to IFNγ only (right) are depicted. See also Supplementary Fig. S3.