Fig. 7: USP5 expression defines the clinical outcome in anti-PD-1 /PD-L1 immunotherapy.

Representative USP5 protein staining of tumor sections (top: 100×, bottom: 400×) (left) and CT scans (right) from liver cancer patients (a) or lung cancer patients (b) undergoing anti-PD-1 treatment. CT scans of patient tumors are shown. c, d Waterfall plot depicting the responses to anti-PD-1 treatment based on the best change in the sum of target lesions compared to baseline in cancer patients with low USP5 or high USP5 expression. Each bar represents one patient, and the colors correspond to the response to anti-PD-1 treatment (PR: partial response, SD: stable disease, PD: progressive disease). Dotted black lines indicate the response as described by RECIST1.1. e, f Pie charts illustrating the response fractions for each group of patients with USP5-low and USP5-high expression in tumor cells. g IB analysis of indicated proteins derived from two fresh HCC samples (HCC180328 and HCC191017) before the establishment of the humanized mouse model. h IB analysis of indicated proteins in a subcutaneous humanized mouse model after 21 days of treatment with anti-IgG or anti-PD-1. i A working model for targeting USP5 to sensitize tumors to PD-1/PD-L1 blockade. USP5 downregulates PD-L1 and enhances the immunosuppressive response, leading to resistance to PD-1/PD-L1 blockade (Left Panel). Inhibition of USP5 by WP1130 upregulates PD-L1 and reduces the immunosuppressive response to sensitize the tumor to anti-PD-1/PD-L1 immunotherapy (Right Panel). All IB data are representative of two independent experiments. Source data are provided as a Source Data file.