Of 479 records identified, 386 unique citations were screened, 127 underwent full‐text review, and 40 met inclusion criteria for qualitative synthesis.<h4>Results</h4>Prospective and institutional studies in biomarker-unselected diffuse midline glioma, high-grade glioma, medulloblastoma, and ependymoma showed low objective response rates (generally ≤ 6%), short median progression-free survival (1-3 months), and overall survival similar to historical controls, despite acceptable safety (grade ≥ 3 treatment-related adverse events ~ 15-25% with anti-PD-1 ± anti-CTLA-4). The gene discussed is CTLA4; the disease is diffuse midline glioma.