...the TMB level was significantly higher in PAPPA2-Mut tumours in the SKCM set (p < 0.001, Figure 4I). In addition, a significant longer PFS was observed in patients with TMB-H and PAPPA2-Mut compared to those with TMB-L and PAPPA2-WT (HR, 0.45 [95% CI, 0.25–0.80]; p = 0.006; Figure 4I–K). Among all patients in the SKCM set, those with TMB-H or PAPPA2-Mut (66/210) achieved significantly longer OS (HR, 0.51 [95% CI, 0.34–0.76]; p < 0.001; Figure 4L)....Our results demonstrated that patients with PAPPA2 mutation were associated with better clinical outcomes in ICIs treatment via activated immunogenicity and enhanced anti-tumour immunity. Thus, PAPPA2 mutation could act as a potential predictive biomarker for ICIs therapy in NSCLC and SKCM.