The interplay of Glioma-associated blood vessels with Microglia and Monocyte-derived macrophages.
2Sagol School of Neuroscience, Tel Aviv University, Israel
Gliomas account for 33% of brain tumors and currently have no effective treatment. The tumor microenvironment (TME) plays a crucial role in the progression of the disease. Two inhabitants of the TME are tumor-associated microglia (TA-MG) and monocyte-derived macrophages (MDM), considered a tumor progression driving force. Yet, their tumoral spatiotemporal distribution and interaction with other components of the TME, such as blood vessels, are poorly understood. This was mainly due to the lack of an efficient approach to discriminate between TA-MG and MDM. In our research, we used a genetic lineage tracing approach and a murine glioma model to reveal the difference in the behavior of TA-MG and MDM in glioma. Here I describe our results regarding the distribution of TA-MG and MDM relative to blood vessels. A machine-learning classification approach allowed us to automate the process of determining the presence of TA-MG and MDM in the different brain region and their density at different blood vessel distances. Our results show that MDM were present only inside the tumor, whereas TA-MG accumulated both outside and inside the tumor. However, TA-MG were eliminated from the tumor mass as the tumor progressed. TA-MG and MDM were enriched in the perivascular area (PVA) compared to areas more distal to blood vessels. However, MDM enrichment in glioma`s PVA was higher than that of TA-MG. Collectively, we show here that TA-MG and MDM exhibit different spatiotemporal features in glioma and their interaction with blood vessels, suggesting a complex and distinctive role during tumor progression.