We collected 75 NSCLC patients who received ICI treatment with WES data as the discovery cohort....Patients with high TMB level were more likely to benefit from the immunotherapy, which was also observed here (Figure 2F). Notably, AHNAK2 mutation could identify patients with better response to immunotherapy among TMB-high patients (Figure 2G), indicating that the combination of AHNAK2 mutation and TMB level could better stratify patients to identify those who are likely to benefit most from immunotherapy...we proposed that del-AHNAK2mut could serve as a novel biomarker for NSCLC patients with ICI treatment. Predictive biomarkers to ICIs, such as the TMB level, NAL level, and TIICs, are closely associated with deleterious AHNAK2 mutations.