Extended Data Fig. 10: Disruption of KAT8-IRF1 condensates by 2142-R8 enhances antitumor immunity.
a, Schematics of the amino acid sequences of the peptides. b, Representative confocal images showing the infiltration of the FITC-2142-R8 in 143B cells. The experiments were repeated three times with similar results. c, CCK8 assay for the peptide cytotoxicity in A375 cells. n = 3 biologically independent experiments. Data are shown as the mean ± SD. p values were calculated by two-tailed Student’s t-test. d,e, Western blot (d) and qRT-PCR (e) analysis of PD-L1 expression in A375 cells expressing indicated sgRNAs treated with 10 μM peptides for 24 h and 100 U/mL IFN-γ for 6 h before harvest. Data are shown as the mean ± SD, n = 3 biologically independent experiments. p values were calculated by two-tailed Student’s t-test. f,g, Western blot (f) and qRT-PCR (g) analysis of PD-L1 in gene-edited IRF1 K78R cells after 10 μM peptides treatment with or without IFN-γ stimulation for 6 h. Data are shown as the mean ± SD, n = 3 biologically independent experiments. p values were calculated by two-tailed Student’s t-test. h, Representative confocal images of cryostat sections showing the infiltration of the FITC-2142-R8 peptide in LLC1 tumor tissues in immune-competent mice. The experiments were repeated twice with similar results. i, The Mean Fluorescence Intensity (MFI) of the IFN-γ + , IL2 + cells and Granzyme B + cells in the tumor infiltrated CD8 + T cells. Data are shown as the mean ± SD, n = 6 mice per group. p values were calculated by two-tailed Student’s t-test. j-l, Mice bearing LLC1 (j), CT26 (k), 4T1 (l) tumors were treated with 5 mg/kg peptide and 100 μg antibody as indicated. The endpoint tumor weights and tumor volumes were plotted. Data are shown as the mean ± SD, n = 6 mice per group, p values of tumor volumes were calculated by Two-way ANOVA with Tukey’s multiple comparisons test. p values of tumor weights were calculated by two-tailed Student’s t-test. m, NOG mice bearing LLC1 tumors were treated with normal saline (NS) or 5 mg/kg peptides; Tumor weights and tumor volumes were measured. n = 6 mice per group. Data are shown as the mean ± SD, p values were calculated by two-tailed Student’s t-test.
