Experimental study of glioma stem cell-mediated immune tolerance in tumor microenvironment / 中华肿瘤杂志

ABSTRACT

Objective@#To investigate the tumor microenvironment of immune tolerance induced by glioma stem cells (GSC).@*Methods@#Human GSC SU3 cells transfected with red fluorescent protein (SU3-RFP) gene were implanted into the brain, subcutis (armpit and foot), liver and abdominal cavity of transgenic green fluorescence protein (GFP) nude mice to establish RFP+ /GFP+ dual fluorescence solid tumor model. The re-cultured cells derived from implanted tumor tissues, SU3-RFP cells co-cultured with peritoneal fluid of transgenic GFP nude mice and malignant ascites of tumor-bearing mice were observed by fluorescence microscopy and real-time video image tracing to analyze the microenvironment of immune tolerance mediated by RFP+ /GFP+ implanted tumor.@*Results@#Dual fluorescence labeled frozen section showed that all of cells in the tumor microenvironment were GFP+ , while the pressed tissue-patch showed that the tumor blood vessels exhibited a RFP+ /GFP+ double-positioning yellow. In the GFP single fluorescence labeled tumor tissue, all of cells in the microenvironment were green, including tumor edge, necrotic foci and blood vessel. Among them, CD68+ , F4/80+ , CD11c+ , CD11b+ and CD80+ cells were observed. In the dual fluorescence labeled co-cultured cells, the phagocytosis and fusion between green host cells and red tumor cells were also observed, and these fusion cells might transfer to the malignant dendritic cells and macrophages.@*Conclusions@#The tumor microenvironment of immune tolerance induced by GSC is not affected by the tissue types of tumor-inoculated sites, and the immune tolerance mediated by inflammatory cells is associated with the inducible malignant transformation, which may be driven by cell fusion.