In summary, tumor-intrinsic alterations such as loss of antigen presentation, defective interferon signaling, and oncogenic mutations (e.g., KRAS/LKB1, PTEN) collectively limit the clinical efficacy of PD-1/PD-L1 blockade in NSCLC, highlighting the necessity of integrating genetic profiling into immunotherapy design. Here, CD274 is linked to non-small cell lung carcinoma.