The Role of Myeloid-derived Suppressor Cells and Non-tumor Cells in theGlioma Microenvironment

Abstract: Glioma, the most common primary brain tumor, is associated with a poor prognosis largely due to the immunosuppressive environment it creates, which allows it to evade immune surveillance. A key component of this immunosuppressive system is myeloid-derived suppressor cells (MDSCs), a heterogeneous population of early myeloid progenitor and precursor cells. Despite their phenotypic and functional diversity, MDSCs consistently exhibit strong immunosuppressive properties. In glioma tissues, MDSCs are widely infiltrated and play a crucial role in suppressing immune responses within the tumor microenvironment, thereby significantly diminishing the efficacy of immune-based therapies. This review explores the phenotypic characteristics of MDSCs in the glioma microenvironment and their mechanisms of action in promoting glioma progression, providing valuable insights into the pathogenesis of glioma and potential comprehensive treatment strategies. In addition to MDSCs, the glioma microenvironment is composed of various non-tumor cells, including endothelial cells (ECs), pericytes, microglia/macrophages, mesenchymal cells, astrocytes, and neurons, as well as soluble cytokines. These non-tumor cellular components interact with glioma cells to form a complex ecosystem that regulates the malignant progression of the tumor. Advances in understanding the glioma microenvironment have opened avenues for developing novel therapies that target these non-tumor cells, potentially improving the prognosis for glioma patients. This review also summarizes the relationship between glioma cells and various non-tumor cells, highlights relevant translational studies, and discusses the future challenges and opportunities in glioma treatment based on the tumor microenvironment.