Outcomes of immunotherapy in medulloblastoma: a systematic review

Abstract Background Medulloblastoma is the most common malignant brain tumor in children. Medulloblastoma has intrinsic characteristics that pose significant challenges to effective immunotherapy. Nevertheless, several clinical trials have explored immunotherapeutic strategies in patients diagnosed with medulloblastoma. This systematic review aimed to synthesize all immunotherapy modalities investigated in medulloblastoma and reported clinical outcomes. Methods A systematic search was conducted in PubMed, Scopus, Web of Science, and ClinicalTrials.gov from inception to 30 June 2025 using the terms “immunotherapy” and (“brain tumor”, “pediatric brain tumor”, or “medulloblastoma”). Original articles, clinical trials, and conference abstracts evaluating any immunotherapeutic intervention in patients with medulloblastoma were included. Risk of bias was assessed using JBI critical appraisal tools. Results Fifty-six studies met the inclusion criteria, encompassing at least 183 patients with medulloblastoma. Nearly half were Phase I trials (24/56, 43%), and 18% (10/56) were non-trial designs. Among the 29 studies reporting clinical outcomes, adoptive cellular therapies in combination regimens (7/29, 24%) and immune checkpoint inhibitors (6/29, 21%) were most frequently evaluated. Overall, clinical benefit was limited. Median overall survival ranged from 1.29 to 47 months, and median progression-free survival from 0.79 to 11 months. Progressive disease was reported in 40 patients, partial responses in 13, and complete responses in three patients. Conclusions Despite increasing trial activity, immunotherapy has shown modest efficacy in patients with medulloblastoma. Interpretation is limited by small cohorts, heterogeneity, and inconsistent reporting of outcomes. Future studies should prioritize rational antigen selection, molecular subgroup stratification, and improved trial design.