Immunotherapy in Medulloblastoma: Current State of Research, Challenges, and Future Perspectives

SIMPLE SUMMARY: Medulloblastoma (MB) is a primary brain tumor and is one of the most prevalent neoplasms in the pediatric age group, with a median age of diagnosis of six years. Besides the symptoms that can accompany BM tumors, conventional therapy involving surgical resection, radiotherapy and chemotherapy can result in severe brain damage and, even with this aggressive, multimodal therapy, the disease is characterized by high relapse rates. As an alternative to the damaging conventional therapies, the use of immunotherapy in MB has gained interest. Different types of immunotherapy, including cancer vaccines, oncolytic viruses, CAR T-cells, and immune checkpoint inhibitors have been studied in in vitro and in vivo models of MB as well as in clinical settings. This review will elaborate on the current state of research concerning immunotherapy in MB, with a special focus on immune checkpoint inhibition and CAR T-cell therapy. ABSTRACT: Medulloblastoma (MB), a primary tumor of the central nervous system, is among the most prevalent pediatric neoplasms. The median age of diagnosis is six. Conventional therapies include surgical resection of the tumor with subsequent radiation and chemotherapy. However, these therapies often cause severe brain damage, and still, approximately 75% of pediatric patients relapse within a few years. Because the conventional therapies cause such severe damage, especially in the pediatric developing brain, there is an urgent need for better treatment strategies such as immunotherapy, which over the years has gained accumulating interest. Cancer immunotherapy aims to enhance the body’s own immune response to tumors and is already widely used in the clinic, e.g., in the treatment of melanoma and lung cancer. However, little is known about the possible application of immunotherapy in brain cancer. In this review, we will provide an overview of the current consensus on MB classification and the state of in vitro, in vivo, and clinical research concerning immunotherapy in MB. Based on existing evidence, we will especially focus on immune checkpoint inhibition and CAR T-cell therapy. Additionally, we will discuss challenges associated with these immunotherapies and relevant strategies to overcome those.