The Effects Upon Tumor Cells Of Regulation And Control Functions From HBx To PPM1a-TGF-? And PD-1/PD-L1 To NK Cells

Objective: This paper mainly studies the effects upon tumor cells of regulation and control functions from HBx to PPM1a—TGF-? and PD-1/PD-L1 to NK cells.Methods : We selected cell lines,plasmids,tissue microarrays and necessary instruments and equipment to carry out the experiments,including cell recovery,cryopreservation and passage,immunoprecipitation,Wwtern Blot detection,immunohistochemistry,and explore the mechanism of HBV infection inducing liver cancer.Selection of nude mice experiments using cell lines and peripheral blood specimens and fresh equipment,experiments,including peripheral blood mononuclear cell separation,human tumor and paracancerous tissue infiltration of mononuclear cells isolated from rat spleen cells,mononuclear isolation,rat subcutaneous tumor infiltrating mononuclear cells into nude mice,separation tumor experiment,immune cell function experiments,tissue slice immunofluorescence and Western Blot experiment,explore the pathogenesis of gastrointestinal tumor.Results:The first part of the experiment showed that activation of TGF-? signaling pathways,HBx decreased the protein levels of PPMla;HBx and TGF-? copromote smart cell migration;exogenous expression of PPMla can promote the migration ability of HBx by reverse HBx;promote proteasome degradation of PPMla can suppress the expression of HBx and PPMla;PPMla clinical specimens from patients with hepatocellular carcinoma into negative correlation.The second part of the experiment results showed that NK cells with high expression of PD-1 indicates poor prognosis in patients with gastrointestinal tumor infiltration and peripheral tumor;PD-1 is involved in the control of NK cell apoptosis in vitro;PD-1/PD-L1 blocking can improve the gastrointestinal function of patients with NK cell;blocking PD-1/PD-L1 can activate PI3K/AKT signaling pathway in NK cells by blocking antibody;PD-1 to enhance the function of NK cells and inhibit the growth of subcutaneous tumor formation in nude mice.Conclusions: This experiment was conducted to explore the mechanism of hepatitis B virus and inflammation related immune microenvironment to promote the development and development of hepatoma and other digestive tract tumors.Through Western Blot detection and immunohistochemistry test,we confirmed that PD-1 and ligand PD-L1 binding were involved in regulating NK cell activation,and also involved in regulating cytotoxic activity.HBx can continuously inhibit PPMla,and the expression level of HBx is positively correlated with the inhibitory effect.HBx and TGF-?have synergistic effect on promoting cell migration.According to the experimental study in mice,the expression of PD-1 in the NK cell surface of the patients with digestive tract tumor was higher than that of the normal human.The up-regulated PD-1 suggests poor prognosis in patients.HBV X protein promotes the development of liver cancer by overactivating the TGF-?signaling pathway by down regulating the phosphatase PPM1 A.PD-1 can lead to poor prognosis in patients with digestive tract tumors by inhibiting the anti swelling cancer immunization of NK cells.The activation of PD-1 downstream signal induces apoptosis of NK cells,and blocking the combination of PD-1 and PD-L1 can inhibit the apoptosis of NK cells.The high expression of PD-L1 in the digestive tract cancer cells,the combination of PD-1 and ligand PD-L1,inhibit the NK cell mediated anti-tumor immunity,and promote the immune escape of tumor cells.Through the study,the PD-1/PD-L1 blockage in the treatment of digestive tract tumors provides a certain reference.