Work

Progression of glioma through PU.1-mediated suppression of macrophage phagocytosis via targeting Siglec-10

Year: 2025

Type: article

Abstract: Macrophage-mediated tumor cell phagocytosis and neoantigen presentation are essential for anti-tumor immunity. This study aimed to investigate the clinical relevance and molecular mechanism of the macrophage-associated transcription factor PU.1 in glioma. Tumor samples from patients with glioma were analyzed along with in vivo and in vitro models using PU.1 knockdown, RNA-seq, quantitative real-time reverse transcription polymerase chain reaction, western blotting, immunofluorescence, flow cytometry, and luciferase/chromatin immunoprecipitation assays to investigate macrophage polarization. PU.1 expression was upregulated in macrophages from glioma tissues compared to those from adjacent normal tissues. Macrophages with PU.1 knockdown exhibited stronger phagocytic ability and inhibited glioma tumor tissue formation in vivo. Mechanistically, PU.1 directly targeted Siglec-10, a key immune checkpoint of macrophage. Our study highlights the pro-tumorigenic role of PU.1 in macrophages and provides experimental evidence regarding the mechanism of the PU.1-Siglec10 axis in modulating immune checkpoint activity within the glioma microenvironment.

Source: International Immunopharmacology

DOI: 10.1016/j.intimp.2025.115718