Overcoming immunotherapy resistance in Group 3 medulloblastoma

Brain tumors are the leading cause of cancer-associated deaths in children. Medulloblastoma (MB) is the most common malignant pediatric brain tumor characterized by four major molecular subgroups including WNT, SHH, Group 3 and Group 4. Group 3 medulloblastoma (G3MB), which features MYC amplification or overexpression, exhibits the worst prognosis and highest rate of metastasis. Currently, surgery, radiation therapy, and chemotherapy are the major treatment options for medulloblastoma. However, there are no FDA-approved targeted therapies or immunotherapies for it. G3MB poses a significant clinical challenge due to its poor response to current treatment regimens, necessitating the investigation of novel therapies. While targeted therapies for G3MB-CDK4/6 inhibitors, HDAC inhibitors and bromodomain inhibitors-are currently being explored, the potential for immunotherapy to make an impact on this stubborn subtype remains under-explored (1). Thus, the goa of this project is to understand the tumor microenvironment (TME) and provide novel immunotherapies to G3MB. We can dissect the TME of human G3MB by performing single-nucleus and spatial transcriptomics on patient specimens acquired from CBTN. This will provide us with clinical-relevant information on how G3MB escapes from immune surveillance.