Fig. 7: Inhibition of NF-κB signaling sensitizes ARID1A-deficient tumors to ICB therapy.
a Representative IB results of ARID1A, p-IKKβ, p-P65 and A20 expression in the lysates of human prostate tumors. Pearson’s correlations among proteins indicated in PCa specimens are summarized in the heatmap (n = 42; GS > 7). b ELISA of CXCL2 and CXCL3 in PCa (n = 42). c Heatmap summary of the correlations of the indicated signature in PCa (n = 150, GSE21032; n = 266, Prad_SU2C_2019). d IHC analysis for ARID1A, P65, CD15 and CD8 markers. Scale bars, 50 μm. The correlations between ARID1A expression and nuclear P65 intensity and the abundance of CD15+ and CD8+ cells are shown as stacked columns (n = 100). e Volume of tumors derived from WT and ARID1A-overexpressing cells injected subcutaneously into FVB mice and treated with IgG and anti-PD1 antibody (n = 10). f Prostate tumor histology of PtenPC−/−; Arid1aPC−/ mice with or without NF-κB inhibition (JSH-23) in combination with anti-PD1/CTLA-4 treatment (n = 10), Scale bars, 50 μm. g IHC staining for Ki67, CD8 and Ly6G and β-Gal in sections by the indicated treatments. Scale bars, 50 μm. h ARID1A functions downstream of inflammation-induced IKKβ activation to shape the immunosuppressive TME through the regulation of NF-κB-mediated chemotaxis. b and e Data represent the mean ± SEM. Statistical significance was determined by two-tailed Pearson’s correlations test (a and c), two-tailed unpaired t-test (b), two-tailed χ2 (d) and two-way ANOVA followed by multiple comparisons (e). g Experiments were repeated at least three times independently with similar results; data from one representative experiment are shown. Source data are provided as a Source Data file.
