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Role of ZBTB18 in cytokine production and microglia phenotype in GBM

ABSTRACT: Glioma associated macrophages (GAMs) are known to play an important role in glioblastoma progression, due to their massive recruitment in the tumor microenvironment and polarization to a tumor promoting phenotype. GAMs secrete a variety of cytokines, which promotes tumor cell growth and invasion while inhibiting an immune tumor response by other immune cells. Here, we demonstrate that ZBTB18, a transcriptional repressor with tumor suppressive function in glioblastoma, impairs the production of key cytokines, which functions as chemoattractant for GAMs. Consequently, we observe a reduced migration of GAMs when ZBTB18 is expressed by GBM cells, both in cell culture and in vivo experiments. Moreover, the presence of ZBTB18 halts GBMs cells-mediated GAMs polarization to a tumor suppressive phenotype characterized by a reduced engage in the oxidative phosphorylation pathway for energy supply. Thus, our findings suggest that therapeutic approaches to increase ZBTB18 expression in GBM cells could have a broad impact on both tumor cells and the surrounding immune microenvironment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE227722 | GEO | 2024/10/08

REPOSITORIES: GEO

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ZBTB18 hinders cytokine expression to impair microglia and macrophage recruitment and the establishment of a tumor-supportive microenvironment in glioblastoma

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