Immunosuppression in Medulloblastoma: Insights into Cancer Immunity and Immunotherapy

Medulloblastoma (MB) is the most common pediatric brain malignancy, with a 5-year overall survival (OS) rate of around 65%. The conventional MB treatment, comprising surgical resection followed by irradiation and adjuvant chemotherapy, often leads to impairment in normal body functions and poor quality of life, especially with the increased risk of recurrence and subsequent development of secondary malignancies. The development and progression of MB are facilitated by a variety of immune-evading mechanisms such as the secretion of immunosuppressive molecules, activation of immunosuppressive cells, inhibition of immune checkpoint molecules, impairment of adhesive molecules, downregulation of the major histocompatibility complex (MHC) molecules, protection against apoptosis, and activation of immunosuppressive pathways. Understanding the tumor-immune relationship in MB is crucial for effective development of immune-based therapeutic strategies. In this comprehensive review, we discuss the immunological aspect of the brain, focusing on the current knowledge tackling the mechanisms of MB immune suppression and evasion. We also highlight several key immunotherapeutic approaches developed to date for the treatment of MB.