Differential Expression of Immunomodulatory Markers in the Tumor Microenvironment of High-Grade Gliomas 2259573

Abstract

Abstract Introduction High-grade IDH-mutant gliomas are increasingly appreciated to have distinct biology in the tumor microenvironment (TME) relative to high-grade IDH-wild-type tumors, including glioblastoma (GBM). Comparative analysis of the TME from different Central Nervous System tumors before treatment is relatively unexplored. Methods To compare these high-grade gliomas, intraoperative ultrasonic aspirate was collected during tumor resection from recently diagnosed patients with GBM or Grade 3/4 Astrocytoma (IDH mutant). High-dimensional flow cytometry was performed using a 5-laser Cytek Aurora, and the differences in the TME between high-grade gliomas grouped by IDH mutation status were evaluated using FlowJo. Immune checkpoint proteins were assessed in well-defined myeloid cell types, including macrophages, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), non-classical monocytes (NCM), and monocytic myeloid-derived suppressor cells (mMDSCs). Additionally, differences in regulatory T cells (Tregs) were examined. Results We found decreased immune suppression markers (CTLA-4) in PMN-MDSC from IDH-mutant Astrocytomas, relative to GBM (55.04% ± 24.56). Decreased immune suppression markers (TIGIT) in M2 polarized monocyte-derived macrophages was also noted in Astrocytomas compared to GBM (44.57% ± 15.54). Conclusion This study allows for in-depth characterization of the TME at the time of surgery, offering unique insight into the immunosuppressive environment. A further understanding of immune system regulation between Central Nervous System tumor types will ideally lead to the development of novel therapeutics for these profoundly immunosuppressive tumors. Funding Source n/a Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)