Experimental Study On The Treatment Of Glioma In Mice By Inhibiting The Glioma Cell Line EFEMP1 And Dendritic Cells With STAT-3 Low Expression

BackgroundNeuroglioma is known as glioma.It is the common neuroepithelial tumor of the central nervous system.The tumors mainly originate from the interstitial cells of the brain,including glial cells,ependymal cells,choroid plexus epithelium and neurons.The treatment of glioma is not static.It is necessary to take into account the origin of tumor,tumor volume and tumor characteristics,and then to select the best treatment plan.It has been proved that the main reason for the growth and proliferation of glioma cells is the low immunogenicity of glioma cells.It is also the main reason for glioma cells to escape the surveillance and killing of immune cells.Secondly,glioma cells have the ability to secrete immunosuppressive factors,these immunosup pressive agents can reduce the killing effect of immune cells on tumor.Therefore,how to improve the immunogenicity of glioma cells,promote the identi fication of glioma antigen,reduce the probability of "immune escape" in glioma cells,prevent the secretion of immunosuppressive factors in glioma cells,improve the killing efficiency of immune cells to glioma cells,these questions have become the key point in the research of glioma immunotherapy.EFEMP1(Fibulin-3),it is mainly distributed on the cell surface and between cells.Its main function is participating in the regulation of the physiological activities of cells and keeping the extracellular matrix structure stable and complete.Many studies have demonstrated that EFEMP1 is involved in the regulation of tumor cell growth and movement.In the study of the correlation between glioma and EFEMP1,it shows that EFEMP1 can indirectly control the growth,proliferation and invasion of glioma cells buy controlling of Notch signaling pathway and matrix metalloproteinase in glioma cells.Therefore,we propose that whether through inhibiting the expression of EFEMP1 in glioma cells can reduce the viability of glioma cells and reduce the invasion of glioma cells to the surrounding normal brain tissue.This is also the starting point and key point of this experimental research.Dendritic cells(DCs)have the important functions of glioma antigen presenting and assistanting CTL to kill glioma cells.It is found that the STAT-3 of STAT protein family members is closely related to the differentiation and maturation of dendritic cells.The increase of STAT-3 phosphorylation level can inhibit the differentiation and maturation of dendritic cells.The inhibition of STAT-3 activity of dendritic cells can relieve the immunosuppressive effect of IL-10,TGF and VEGF on dendritic cells and increase the level of cytokines secreted by dendritic cells.The aim of this study is to inhibit the expression of EFEMP1 and decrease the expression of STAT-3 in dendritic cells and combine the two strategies.First of all,we establish the animal model by tumor bearing glioma cells with low EFEMP1 expression,and then we prepare the dendritic cell vaccine with STAT3 low level expression by lentivirus transfection,at last the STAT3 low level expression of dendritic cell vaccine is transferred into the tumor bearing animal model.By comparing the survival time of animal model,observing the infiltration of lymphocytes in glioma tissue and recording the spleen index of tumor bearing mice,to verify the immune therapeutic effect by inhibiting glioma cell line EFEMP1 and combining with STAT-3 low expression of dendritic cells.Finally to provide theoretical support for establishing a new strategy in glioma immunotherapy.