CD274 and neoplasm: They are often immunologically "cold" with low tumor mutational burden (TMB) and very few tumor-infiltrating lymphocytes (TILs), which may limit the role of immune checkpoint inhibitors (ICI).<h4>Methods</h4>We performed a PRISMA‐guided systematic review of PubMed/MEDLINE, Embase, and Scopus from inception to September 17, 2025, for English-language studies of patients ≤ 21 years with primary CNS tumors treated with PD‐1/PD‐L1 or CTLA‐4 inhibitors.