A Pilot Exploratory Study On The Role Of A Subpopulation Of Macrophages In Medulloblastoma

Medulloblastoma (MB) is the most common childhood malignant brain tumor. We have previously described the presence of tumor-infiltrating macrophages among patient MBs (n=60). There are diverse subsets of tumor-infiltrating macrophages, we studied one specific subpopulation of macrophage (Subpopulation 1) in MB, and observe that a distinct molecular phenotype of MBs associated with high-macrophage infiltrated MBs. We created an in-vitro system in our laboratory to study the role of macrophages (mixed stages of development) in MB tumorigenesis, using 4 patient-derived primary tumor cell lines in a stimulated versus un-stimulated macrophage environment. Only 1 primary MB cell line demonstrated a higher rate of tumor proliferation in a stimulated environment with macrophages at mixed stages of development. In an un-stimulated environment with macrophages at mixed stages of development, all 4 cell lines did not demonstrate any proliferation differences. After prolonged exposure to MB tumor cells, less mature macrophages are highly attracted towards MB tumor cell microenvironment, while mature macrophages are less migratory. We further refined this in-vitro system to study another subpopulation of macrophages (Subpopulation 2). Subpopulation 2 macrophages in a stimulated environment, demonstrate differential proliferative effects on different MB cell lines. We also observed differential migration of Subpopulation 2 macrophages towards different MB cell lines. We are currently studying the roles of different subsets of the diverse spectrum of macrophages in the tumor microenvironment that affect MB tumor development. This will enable us to identify and target the most important subpopulation of macrophages that promotes aggressive tumor behavior in MB.