Immunotherapy approaches for the treatment of relapsed or progressive medulloblastoma.

purposeImmunotherapy provides a novel and alternative treatment strategy to improve the outcomes in patients with refractory medulloblastoma. Two promising immunotherapies are immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T-cells. In this review, we aim to summarize the available and investigational opportunities for ICI and CAR T-cell therapies, specifically for patients with refractory or relapsed medulloblastoma, tailored to their tumor molecular subtypes.

methodsWe searched the PubMed database and clinicaltrials.gov from January 2010 through October 2025 for studies evaluating treatments for patients with relapsed medulloblastoma.

resultsA point somatic mutation (r.3A>G) in U1, a non-coding snRNA, is found in two-thirds of patients with SHH-α tumors with TP53 mutations and in over 95% of SHH-δ tumors. The U1 mutation leads to altered splicing, potentially causing post-translational hypermutation. Accordingly, these tumors may be responsive to ICI. CAR T-cell therapies have shown promising results in patients with brain tumors. CAR T-cell therapies are designed to target universal tumor epitopes to improve their clinical testing feasibility. However, one challenge to achieving durable tumor control is the existence of treatment-resistant populations driven by intratumor heterogeneity. Therefore, we summarized the expression of available targets in specific medulloblastoma molecular groups to guide therapy selection.

conclusionWe provide a basic understanding of how the medulloblastoma molecular heterogeneity can serve as a window for ICI. Furthermore, we provide a summary of the current and future CAR-T cells being tested for the treatment of different refractory medulloblastoma based on their molecular subtypes.