Fig. 6. Inhibition of USP14 activity increases ICB sensitivity.

a Schematic of tumor inoculation and treatment in mice and representative micrographs of tumors. MC38 cells stably transfected with scramble or usp14 shRNAs were subcutaneously implanted into C57BL/6 J mice at day 0. n = 6 for each group. b Tumor weight of MC38 cells stably transfected with control shRNA or usp14 shRNA in C57BL/6 J mice treated with anti-PD-1 or IgG isotype control. n = 6 for each group. c Survival of the indicated tumor-bearing C57BL/6 J mice treated with anti-PD-1 or IgG isotype control. Log-rank test. n = 6 for each group. d Schematic of tumor inoculation and treatment in mice and representative micrographs of tumors. MC38 cells were implanted into C57BL/6 J mice subcutaneously at day 0. n = 6 for each group. e Tumor weight of MC38 cells in C57BL/6 J mice treated with anti-PD-1, IU1, anti-PD-1 plus IU1, or isotype control. n = 6 for each group. f Survival of MC38 tumor-bearing C57BL/6 J mice treated with anti-PD-1, IU1, anti-PD-1 plus IU1, or isotype control. Log-rank test. n = 6 for each group. g, h The percentage of GzB⁺ cells in CD8⁺ T cells (g) and CD25⁺FOXP3⁺ cells in CD4⁺ T cells (h) isolated from the indicated tumors was measured by flow cytometry and analyzed by FlowJo software. i The percentage of PD-1⁺ cells in CD8⁺ T cells isolated from the indicated tumors was measured by flow cytometry and analyzed by FlowJo software. j Quantification of GzB⁺CD8⁺ cells and FOXP3⁺CD4⁺ cells analyzed by IF staining in tumors (n = 3 biological replicates). k The percentage of GzB⁺CD8⁺ T cells and CD4⁺CD25⁺FOXP3⁺ T cells per milligram of the indicated tumors was measured by flow cytometry and analyzed by FlowJo software (n = 3 biological replicates). l Ratio of GzB⁺CD8⁺ T cells to Tregs in the indicated tumors. In g–l error bars represent the mean ± SD of three independent experiments. In b, e, and g–l, two-sided Student’s t-test. GzB Granzyme B. Source data are provided as a Source Data file.