CBIO-05UNDERSTANDING AND TACKLING PARACRINE SIGNALING CUES BETWEEN GLIOMA AND IMMUNE CELLS TO THWART GLIOMA INVASIVENESS AND ANGIOGENESIS

Glioblastoma multiforme (GBM) is the most belligerent adult brain tumor, which is defined by its aggressive growth due to uncontrolled cellular proliferation, resistance to apoptosis, diffuse infiltration and invasion, propensity for necrosis and hypoxia, and vigorous angiogenesis. Recurrence of these invasive tumors is inevitable despite advanced multimodal therapy with surgery followed by radiation and temozolomide treatment resulting in a dismal median survival of beyond one year. A recent milestone in glioma research has been the revelation that therapies targeting other cell types besides tumor cells; i.e., the cell constituents of the vascular niche can convey substantial improvements in radiographic response, progression-free survival, and quality of life. The changing perspective on the environment as a functional contributor represents a profound shift in the approach to biology and therapeutic decisions in GBM. Here, by studying paracrine signaling cues of intratumoral myeloid cells in the perivascular tumor niche and microglial cells in the invading tumor niche we found that these two immune cell populations have distinct and different functions with microglial cells playing a pivotal role in tumor cell invasiveness while intratumoral myeloid cells regulate angiogenesis and tumor survival. Importantly, blocking immune cell-tumor cell paracrine signaling cues endorsed an immunestimulatory and angiostatic environment and ceased tumor invasiveness.