Clinically, p16/p21 co-expression patterns predict immunotherapy efficacy: NSCLC patients with low p16 expression exhibit elevated PD-L1 levels but paradoxically inferior responses to PD-1 inhibitors, suggesting p16 loss primes an immune-evasive phenotype resistant to checkpoint blockade (91). This evidence concerns the gene CDKN2A and non-small cell lung carcinoma.