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Expression And Immunolocalization Of Co-stimulatory Molecule B7-H4 In Gastric Cancer Tissues

Posted on:2016-05-12Degree:MasterType:Thesis
Country:ChinaCandidate:M Y CaiFull Text:PDF
GTID:2284330464950465Subject:Immunology
Abstract/Summary:
Gastric cancer is one of the main malignant tumors threaten human health. Despite of the increasing means and improving therapeutic level, the therapeutic effect is still not ideal. Consequently, it is very urgent to find a new diagnostic and prognostic marker for gastric cancer and to explore new treatment strategies.Negative co-stimulatory molecule B7-H4 is a new member of the B7 family, which is mainly expressed in macrophages, mature dendritic cells, some tumor cells and activated T cells. It can negatively regulate T cell immune responses by inhibiting T cell proliferation, cytokine production and cell cycle progression, and play an important role in the process of mediating tumor immune responses. In recent years, the study of the tumor microenvironment and immune escape has demonstrated that B7-H4 could be abnormally expressed in numerous human tumors as well as infiltrating immune cells, and play an important role in tumor immune escape as an important part of tumor microenvironment. B7-H4 can negatively regulate the T cell mediated anti-tumor immunity and regulate the biological function of the tumor cells, which contributes to the tumorigenesis and tumor progression.In this study, the expression and immunolocalization of B7-H4 in gastric cancer tissues, gastric cancer infiltrating immune cells and peripheral blood mononuclear cells were detected by immunohistochemistry, immunofluorescence staining, confocal scanning and flow cytometry, thus laying the foundation for the further study on the molecular mechanism of B7-H4 in the process of the tumorigenesis and progression of gastric cancer.Objective: To investigate the expression and localization of the negative co-stimulatory molecule B7-H4 in the tissues and in the infiltrating immune cells subsets of patients suffering from gastric cancer.Methods: Immunohistochemistry, immunofluorescence staining and confocal scanning methods were used to characterize the expression and immunolocalization of B7-H4 protein in gastric cancer tissues. Flow cytometry was used to characterize the B7-H4 expression in the peripheral blood mononuclear cell subsets in gastric cancer patients.Results: The immunohistochemistry and confocal scanning results showed that the positive immunolocalization of B7-H4 was positively expressed in gastric cancer tissues, which was mainly located on the cell membrane. Especially the membranous staining of B7-H4 could be found in Ki67 positive highly proliferating gastric cancer cells. It was found that B7-H4 was also highly expressed in CD34 positive endothelial cells of neo-vessels, infiltrating CD19 positive B cells and CD68 positive macrophages, while the weak immunolocalization of B7-H4 protein could be found in infiltrating CD4 positive T cells, CD8 positive T cells and CD57 positive NK cells. The flow cytometry analysis showed that positive B7-H4 expression could be found in the peripheral blood infiltrating CD19 positive B cells and granulocytes of gastric cancer patients, while B7-H4 was weakly expressed in infiltrating CD3 positive T cells and CD14 positive monocytes.Conclusions: It is suggested that B7-H4 could be expressed in tumor cells and some infiltrating immune cells of gastric cancer tissues. B7-H4 can be considered as a potential target for the diagnosis, treatment and prognosis of gastric cancer.
Keywords/Search Tags:Co-stimulatory molecule, B7-H4, Gastric cancer, Immunohistochemistry, Immunofluorescence staining, Confocal scanning, Flow cytometry
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