Abstract： Objective To determine the effect of melatonin on the immune evasion of glioma cells and the underlying mechanism.Methods Three glioma cell lines were used and treated with melatonin of different concentrations.The cells were pretreated with IFN-γ to imitate the immune microenvironment of glioma and cocultured with peripheral blood mononuclear cell(PBMC).The cell viability was determined by CCK-8 assay.The total and membrane PD-L1 protein were detected by Western blot and flow cytometry,respectively.Survived glioma cells were stained by crystal violet assay.Results Melatonin inhibited the cell viability of T98G,U251,and U118 glioma cells in a dose-dependent manner.No significant changes were observed in the total or membrane PD-L1 expression of melatonin-treated glioma cells in a normal environment.Nevertheless,under the IFN-γ induced immune microenvironment,melatonin remarkably down-regulated both the total and membrane expression of PD-L1 and attenuated the immune evasion of glioma cells shown by notably eliminated glioma cells by PBMCs.Conclusion Melatonin may attenuate the immune evasion of glioma cells by down-regulating the expression of PD-L1 in glioma cells,which provides evidence for the application of melatonin in glioma treatment.