Despite these findings, patients with advanced NSCLC and active brain metastases are often underrepresented in, or excluded from, clinical trials.2, 3, 4, 5, 6 Recent studies have shown fewer tumor-infiltrating lymphocytes and T-cell clones and less programmed death-ligand 1 (PD-L1) expression in brain metastases than in paired primary lung cancers,7,8 suggesting the potential for differential response to immunotherapy among patients with and without brain metastases. The gene discussed is CD274; the disease is non-small cell lung carcinoma.