TAMing Gliomas: Unraveling the Roles of Iba1 and CD163 in Glioblastoma

Gliomas, the most common type of primary brain tumor, are a significant cause of morbidity and mortality worldwide. Glioblastoma, a highly malignant subtype, is particularly common, aggressive, and resistant to treatment. The tumor microenvironment (TME) of gliomas, especially glioblastomas, is characterized by a distinct presence of tumor-associated macrophages (TAMs), which densely infiltrate glioblastomas, a hallmark of these tumors. This macrophage population comprises both tissue-resident microglia as well as macrophages derived from the walls of blood vessels and the blood stream. Ionized calcium-binding adapter molecule 1 (Iba1) and CD163 are established cellular markers that enable the identification and functional characterization of these cells within the TME. This review provides an in-depth examination of the roles of Iba1 and CD163 in malignant gliomas, with a focus on TAM activation, migration, and immunomodulatory functions. Additionally, we will discuss how recent advances in AI-enhanced cell identification and visualization techniques have begun to transform the analysis of TAMs, promising unprecedented precision in their characterization and providing new insights into their roles within the TME. Iba1 and CD163 appear to have both unique and shared roles in glioma pathobiology, and both have the potential to be targeted through different molecular and cellular mechanisms. We discuss the therapeutic potential of Iba1 and CD163 based on available preclinical (experimental) and clinical (human tissue-based) evidence.