Factors of TMB (HR, 0.35 [95% CI, 0.22–0.58]; p < 0.001; Table 1) and PD-L1 (≥50%; HR, 0.38 [95% CI, 0.17–0.86]; p = 0.02; Table 1) were also significantly associated with superior PFS. In 100 patients with known PD-L1 status, 35.3% and 16.9% had PD-L1 ≥50% in patients with PAPPA2-Mut and PAPPA2-WT, respectively (Figure S1A). Patients with positive PD-L1 expression (≥1%) and PAPPA2-Mut tended to have a superior PFS (HR, 0.11 [95% CI, 0.02–0.46]; p = 0.003; Figure S1B)....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.