Despite successes in treating childhood cancer, outcome remains poor for children and adolescents with advanced solid tumors, including brain tumors and sarcomas. We study a protein called Cdk5 in medulloblastoma, and our preliminary data indicate that tumors become vulnerable to immune cell killing when Cdk5 function is disrupted, and this disruption, which can be achieved by drugs currently being tested in Phase I clinical trials, was correlated with a diminished production of immune-protective molecule called PD-L1 on tumor cells. We will identify the mechanisms by which Cdk5 confers immune evasion capacity of solid cancers in order to enhance immunotherapy treatments.