Here, we used lung cancer cell lines, patient samples, The Cancer Genome Atlas (TCGA) databases, and syngeneic murine models to comprehensively investigate the clinical relevance between TSC1/TSC2 status and the immune characteristics of NSCLC and the efficacy of ICB therapy in TSC1/TSC2-deficent NSCLC. The gene discussed is TSC2; the disease is non-small cell lung carcinoma.