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 Project objective

One of the key goals to understand GBM biology and find strategies to treat this deadly tumor is to define the different cell populations within the tumor. The inter-tumor heterogeneity among GBM patients, investigated on a molecular level, has led to the identification of three main subtypes; the proneural (PN), mesenchymal (MES), and classical (CL), which are associated with specific mutations. The different properties of the three subgroups play an important role in the clinical response and the pathology of the tumor. The tumor microenvironment, that play an important role in tumor heterogeneity, is built up by multiple factors including recruited cells, blood vessels, secreted cytokines, and extracellular matrix. However, the constitution of these factors in each subtype is not known. In this work, we will characterize the cells that are recruited to the different GBM subtypes focusing on tumor-associated macrophages (TAMs) and mesenchymal stromal cells (MSCs). For this purpose, transgenic mice representing the three glioma subtypes will be used. Chimeric mice will be utilized to investigate the origin of the recruited cells. Flow cytometry, confocal analysis, multiplex assays and single-cell gene expression analysis will be used to characterize the tumor cells and the recruited cells to find master regulatory elements of recruitment. Therapeutic targeting will follow identification of master regulatory factors that recruit TAMs and MSCs to the tumor.