Abstract:Objective : To explore the molecular mechanism of macrophage polarization in tumor treatment by
studying the effect of macrophage colony stimulating factor 1 receptor(CSF-1R) inhibitor BLZ945 on malignant
glioma. Methods : Brain stereotaxic apparatus was used to construct an animal model of malignant glioma. Thirty
male Wistar rats aged 5-6 weeks were randomly divided into 3 groups( 10 in each group): the malignant glioma
animal model group( C6 group), the BLZ945 low dose treatment group( Low dose group), and the BLZ945 high
dose treatment group( High dose group). Survival ratio was observed and recorded. After the treatment, the rats
were sacrificed, and the whole brain was taken by craniotomy and weighed, and the tumor volume was measured
and calculated. The immunophenotype of macrophage was detected by flow cytometry. The transcription level of
interferon-γ(IFN-γ) and suppressor of cytokine signaling 3(SOCS3) mRNA was detected by reverse transcriptionpolymerase
chain reaction. Protein expression level of IFN-γ and SOCS3 was measured by enzyme-linked
immunosorbent assay. Results : BLZ945 could significantly inhibit the growth of malignant glioma and improve
the survival ratio of tumor-bearing mice. BLZ945 could induce the polarization of macrophage to M1 type in tumor
microenvironment, and it could up-regulate the expression of IFN-γ and down-regulate the expression of SOCS3
in tumor tissues. Conclusions : BLZ945 induces the polarization of macrophage from M2 to M1 by regulating the
expression of IFN-γ and SOCS3, activates anti-tumor immunity, and then inhibits the growth of malignant gliomas.