PD-L1 expression and tumor mutational burden (TMB) have been deeply investigated as ICIs predictive biomarkers in different randomized trials.9, 10, 11 However, despite the approval of PD-L1 expression as a standard biomarker for ICIs in the management of advanced NSCLC patients,1,7 response prediction was revealed to be imperfect with a not-negligible percentage of patients experiencing resistance either at baseline or during treatment.12 This evidence concerns the gene CD274 and non-small cell lung carcinoma.