Fig. 8: Cancer patients with low USP2 expression exhibit better responses to cancer immunotherapy.

a, b Representative IF staining images for CD163 (green) and CD8 (red) in human lung adenocarcinoma (LUAD) tissues with the USP2 high (n = 13) and low (n = 16) expression (a). Quantifications of CD163 and CD8 positive cells in LUAD samples with USP2 high or low expression, respectively (b). Each point represents the average counts of positive cells within three high-power fields. Scale bars, 500 μm (left panels); zoom scale bars, 50 μm (right panels). c–e USP2 expression was negatively correlated with the infiltration of M1 macrophages (c) and CD8⁺ T cells (e), while USP2 displayed a positive correlation with the infiltration of M2 macrophages (d) in lung cancer patients based on the immune association analysis by TIMER2.0 software. f, g Representative images from IHC staining of CD47 and USP2 in responders (R) and non-responders (NR) of lung cancer patients with anti-PD-1 therapy (f). Scale bar, left panels: 100 μm; right panels: 50 μm. Association between USP2 or CD47 expression and response to anti-PD-1 therapy in lung cancer patients (g). n = 6 (R), or 6 (NR). Patients were divided into USP2 or CD47 low and high expression groups according to their IHC score mean value (f). h, i Representative images of multiplex immunohistochemistry (mIHC) staining for R and NR of lung cancer patients with anti-PD-1 immunotherapy (h). Quantifications of CD163 (white), CD8 (red), and CK (green) in each group (i). Each point represents the average counts of positive cells within three high-power fields. n = 5 per group. Scale bars, 100 μm (left panels); zoom scale bars, 50 μm (right panels). j, k Representative images from IHC staining of CD47 and USP2 in responders and non-responders of oral cancer patients with anti-PD-1 therapy (j). Scale bar, left panels: 100 μm; right panels: 50 μm. Association between USP2 or CD47 expression and response to anti-PD-1 therapy in oral cancer patients (k). n = 25 (R), or 19 (NR). Patients were divided into USP2 or CD47 low and high expression groups according to their IHC score mean value (j). l, m Representative images of mIHC staining for responders and non-responders of oral cancer patients with anti-PD-1 therapy (l). Quantifications of CD163 (white), CD8 (red), and CK (green) in each group (m). Each data point represents the average counts of positive cells within three high-power fields. n = 18 (R), or 13 (NR). Scale bars, 100 μm (left panels); zoom scale bars, 50 μm (right panels). For (b), unpaired two-tailed Student’s t-test. For (g) and (k), a two-sided χ² test. For (i) and (m), two-tailed Non-parametric Mann–Whitney test. Data are shown as the mean ± SD P < 0.05 was considered statistically significant. Source data are provided as the Source Data file.