We are members of INDUCER- Increasing Diversity in Undergraduate Cancer Biology Education & Research. Our program strives to give opportunities to experience cancer research to underrepresented students interested in the biomedical sciences. We want to help bridge the gap in medicine between Caucasians and People of Color and combat racial disparity. We utilize the GL261 cell line in the murine model to study and understand glioblastomas and their tumor microenvironment, which includes microglia and macrophages. Microglia function as macrophages of the central nervous system, play a critical role in the innate and adaptive responses to pathogens and can take on a pro-inflammatory/anti-tumorigenic (M1) or anti-inflammatory/pro-tumorigenic (M2) phenotype. Our research introduces Colony Stimulating Factor 1 Receptor (CSF1R), which is expressed by both microglia and macrophages, whose signaling is critical for their proliferation and survival. Pexidartinib is a CSF1R inhibitor drug developed by Plexxikon Inc (PLX), a pharmaceutical company. They have generated PLX3397 and PLX5622. Each drug inhibits specific kinases, for example, PLX3397 inhibits c-KIT, CSF1R, and FLT3, which are key players in tumor proliferation, while PLX5622 is a specific inhibitor that only targets CSF1R signaling. Both PLX3397 and PLX5622, provided to mice in their chow, ablate microglia in the CNS of wild type mice, without affecting peripheral macrophages. Upon discontinuation of the diet, microglia repopulate the CNS. PLX73086 is a second generation CSF1R inhibitor, and little is known about its effects on microglia and macrophages. What is known is that it should only ablate macrophages in the periphery, not affecting the CNS because it is not expected to cross the Blood Brain Barrier. Upon the discontinuation of the diet, repopulation is similarly expected. In our research, we studied the effects of PLX73086 on macrophages and microglia of the murine glioma model, after being fed the diet for 7 days and 7 days off the diet. We compared the extent of ablation and repopulation of the tissue.

Citation Format: Maryam Tayyab, Maame Gyamfi, Michael Caponegro, Dr. Styliani-Anna (Stella) Tsirka. Investigating the Interplay of monocytes in the tumor microenvironment of glioblastomas [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D065.