Fig. 4

Immune/metabolism score as a potential predictive biomarker for immunotherapy response. a Heatmap showing the ssGSEA scores of immune signatures and metabolic pathways in patients stratified into ‘immune-dominant’ (left, pink) and ‘metabolic-dominant’ (right, purple) subgroups. The color scale represents the normalized expression values. b Proportion of patients in the immune-dominant (ID) and metabolic-dominant (MD) subgroups within the non-responder (NR) and responder (R) groups. c Heatmap displaying the expression levels of the six genes used to calculate the immune/metabolism (I/M) score in responders and non-responders. d Representative mIHC images of tumor samples from patients with different BOR in BTC and PDAC patients. Color-coded for immune cell populations was as illustrated, with the TLS region circled by a dashed line. The scale bar at the bottom left corner of the mIHC images represents 0.1 mm. TLS, tertiary lymphoid structure; SD, stable disease; PD, progressive disease. e Comparison of I/M scores between non-responders (NR) and responders (R; P = 0.0079, Mann-Whitney U test). f Kaplan-Meier curves for overall survival (OS) stratified by I/M score group (high vs. low), with median OS and P value (0.0252, log-rank test). The number at risk table was included. g External validation cohort 1 (n = 289, IMvigor210): I/M scores in R vs. NR (left; P = 2.8e-08, Mann-Whitney U test), and OS stratified by I/M score group (high vs. low) with median OS, P value (2.55e-08, log-rank test), and number at risk table (right). mUC, metastatic urothelial carcinoma. h Scatter plot showing the correlation between I/M score and tumor regression change in non-responders (NR, blue) and responders (R, red). Spearman correlation coefficient (r) = 0.592, with a P value of 1.2e-02. i Receiver operating characteristic (ROC) curve for the response prediction model using the I/M score. The plot showed the performance of the model in the test cohorts (SHR-1701 plus famitinib, AUC = 0.930; mUC-anti-PD-L1, AUC = 0.727) and three external validation cohorts. AUC area under the curve, mUC metastatic urothelial carcinoma, NSCLC non-small cell lung cancer, STAD stomach adenocarcinoma