| The anti-tumor immune response is a complicated physiological process involving many immunocytes and molecules and subjected to strict regulation and restriction. In recent years, mounting researches showed that the regulatory expression, interactivation and signal transduction among costimulatory molecules play an vital role in the mechanism of anti-tumor immunity. In terms of structure, costimulatory molecules are divided into two categories, TNF-TNFR superfamily and Ig superfamily. The most intensively characterized CMs are those of the B7 family. The classical members of this family B7-1 (CD80) and B7-2 (CD86) interact with and activate CD28 on naive T cells, and stimulate IL-2 production. A number of new members (B7-H1, B7-H2, B7-H3, B7-DC) of the B7 family have recently been identified, and their structures and functions were elucidated. Recent studies showed that some B7 family members such as PD-L1 could be expressed on tumor cells and DCs of tumor tissues and played important role in indicating special T cell apoptosis and tumor immune escape. Among them, B7-H, a newly identified B7 family member is 20~27% homologous with other B7 members. It was found to be capable of costimulating proliferation of CD4~+T cell and CD8~+T cells. In addition, B7-H3 expression was detected on a series lung cancer cells and leukemia cells which aroused great attention in academic circle. Fas ligand (FasL), a type II transmembrane protein, belongs to TNF superfamily. As an important element driving the process of AICD, it was found that fasL was also a key participant in the mechanism of immune escape of tumor cells. Survivin is so far the strongest apoptosis protein inhibitor. Its expression was detected on fetal tissues and most tumor tissues while undifferentiated tissue of adults (expect thymus and sexual glands) do not express surviving.In this study, we analyzed expression of PD-L1, B7-H3, FasL and Survivin ongastric carcinoma tissues, the gastric adenocarcinoma and nonnal gastric tissues to make an initial exploration on its clinical significance.Part IThe Relationship between PD-L1 Expression and HistoiogicalManifestation as well as Prognosis of Gastric CarcinomaAbstract Objective: To study the expression of costimulatory molecules PD-Ll in the gastric_ carcinoma tissues, normal gastric tissues and gastric adenoma tissues and to explore the relationship between PD-L1 expression and pathological features and prognosis of gastric carcinoma. Methods: The PD-L1 expression was detected in 102 samples of human gastric carcinoma and 10 samples of gastric adenoma and 10 samples of normal gastric tissues by immunohistochemistry assay and the correlation analysis had been done between the expression of PD-L1 and the patients' age, sex , gastric carcinoma locus, tumor size, tissue type, tumor infiltration depth, differentiation degree, lymphnode metastasis and survival time and so on. Results: There was no expression of PD-L1 in the normal stomach tissues and tissues of gastric adenoma, instead, 42.2% PD-L1 expression was detected on samples of gastric carcinoma and it was also found that PD-L1 expression on gastric carcinoma tissues had nothing to do with the patients' age, sex, tumor locus, histology type and tumor size (P>0.05), but it was correlated to the infiltration depth of tumor, lymph node metastasis and survival time. Especially when the tumor infiltrated into deep muscular layers or lymph node metastasized or survival time was less than 2 years, PD-L1 was highly expressed (P<0.01). The multivariate analysis manifested that PD-L1 could be regarded as an independent factor in evaluating gastric carcinoma prognosis. Conclusion: PD-Ll highly expressed in gastric carcinoma tissues. Detection of PD-L1 expression in gastric carcinoma tissues will be beneficial to the judgments of the prognosis of gastric carcinoma and the choice of postoperative individualization treatment.Part IIThe Relationship between B7-H3 Expression and Histologicalmanifestation as well Prognosis of Gastric CarcinomaAbstract Objective: To study the expression of costimulatory molecules B7-H3 in the gastric carcinoma tissues, normal gastric tissues and gastric adenoma tissues and to explore the relationship between B7-H3 expression and pathological features and prognosis of gastric carcinoma. Methods: The B7-H3 expression was detected in 102 samples of human gastric carcinoma and 10 samples of gastric adenoma and 10 samples of normal gastric tissues by immunohistochemistry assay and the correlation analysis had been done between the expression of B7-H3 and the patients' age, sex , gastric carcinoma locus, tumor size, tissue type, tumor infiltration depth, differentiation degree, lymphnode metastasis and survival time and so on.. Results: The expression of B7-H3 in gastric adenoma tissues was 100%, instead,there was no B7-H3 expression in gastric normal tissues.58.8% B7-H3 expression was detected in samples of gastric carcinoma tissues and it was also found that B7-H3 expression in gastric carcinoma tissues had nothing to do with the patients' age, sex, lymph node metastasis and tumor size (P>0.05), but it was correlated to the survival time, infiltration depth of tumor and tissue type. If the gastric carcinoma histology type was differentiated and the tumor infiltration was not found at deep muscular layer, B7-H3 was highly expressed ( P< 0.05 ) . And if the survival time was more than five years, B7-H3 was highly expressed ( P<0.01 ) .The multivariate analysis manifested that B7-H3 could be regarded as an independent factor to evaluate gastric carcinoma prognosis. Conclusion: B7-H3 highly expressed in gastric carcinoma tissues.Detection of B7-H3 expression in gastric carcinoma tissues will be beneficial to the judgments of the prognosis of gastric carcinoma and the choice of postoperative individualization treatment.Part IIlThe Relationship between Expression of PD-L1 and B7-H3 in GastricCarcinoma Tissues and the Patients' PrognosisWe analyzed the results of part I and part II and combine the PD-L1 and B7-H3 expression to make a survival curve. We found that the survival curve of those whose PD-L1 expression was negative and B7-H3 expression was positive was obviously detached with that of those whose PD-L1 expression was positive and B7-H3 expression was negative. It suggested that PD-L1 high expression and B7-H3 low expression often indicated t worse prognosis of the gastric cancer patients.Part IVThe Relationship between FasL and Survivin Expression and GastricCarcinoma Histology as well PrognosisAbstract Objective: To study the expression of FasL and Survivin in the gastric carcinoma tissues and their clinic significance. Methods: The FasL and Survivin expression in the gastric adenocarcinoma, normal gastric tissues and gastric carcinoma tissues were detected by immunohistochemistry assay and the correlation analysis had been done between the expression of FasL and Survivin and the patients' age, sex , gastric carcinoma locus, tumor size, tissue type, tumor infiltration depth, differentiation degree and lymphnode metastasis and so on. Results: There was no FasL and Survivin expression in the gastric adenocarcinoma and normal gastric tissues. Instead, 61.8% FasL and 66.7% Survivin expression was detected in samples of gastric carcinoma tissues. It was also found that FasL and Survivin expression on gastric carcinoma tissues had nothing to do with the patients' age and sex (P>0.05). But FasL expression was correlated to lymphnode metastasis, tumor size and tissue type (PO.05) , while Survivin expressionwas correlated to lymphnode metastasis and tumor infiltration depth (PO.05 ) . Conclusion: Detection of FasL and Survivin expression in gastric carcinoma tissues has important significance to the development and prognosis of gastric carcinoma and it willbe a guide to individualized postoperative treatment.
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