The immune microenvironment of medulloblastoma (MB) is being increasingly studied, and a number of pre-clinical immunotherapy studies have shown promise in MB. However, the reality is that these therapies will only be given to MB patients in combination with conventional therapies, such as chemotherapy. The impact of chemotherapy on immune cells in the brain has not previously been investigated. A preliminary study comparing the survival of immune competent C57Bl/6 wild type (WT) and immune-deficient RAG1-/- mice with MB following long-term treatment with gemcitabine (Gem) or cyclophosphamide (CPA) showed an improvement in survival of immune deficient RAG-/- mice treated with Gem. This suggests that the interaction between lymphoid and myeloid immune cells is an important factor in modulating the fate of MB mice receiving chemotherapy. Here, we assessed the effects of CPA and Gem on multiple immune cell populations in the brains of tumour-bearing mice using flow cytometry and immunohistochemistry. The response to Gem appeared to be driven by myeloid cells, and was improved in the absence of T cells. Conversely, in mice treated with CPA, although treatment caused T cell depletion and an increase in monocyte infiltration, there was no improve overall survival. This preliminary data suggests that T cells play an important role in modulating monocyte infiltration and differentiation in MB, which may be crucial for the immune response to chemotherapy. Further investigation is required to understand this potential interaction between the myeloid and lymphoid cells.