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. This evidence concerns the gene CD274 and lung cancer.