| T cell-mediated immune response plays an important role in anti-tumor immunity, T cell activation need double stimulation signal, namely after T cell antigen receptors and tumor antigen, provide the first signal of T cell activation, by antigen presenting cells(APCs) on certain molecules such as cell adhesion molecules, lymphocyte function associated antigen, vascular cell adhesion molecule, and T cells in the corresponding receptors, the second signal can be provided to T cell activation. Coordinated stimulus signal, by antigen presenting cells(APC) for mediating and/or adjust the B7 family of T cell responses were provided stimulus and other stimulus molecules. Synergy stimulus signal is in T cell activation by Bretscher and Cohn 1970 double signal model, is proposed on the basis of that in addition to need through the APC is MHC- antigen peptide compounds give antigen specific T cells outside the first signal, still need a lot of the second signal coordinated stimulus molecules participating in the provision of auxiliary, and gives some physiological activation threshold, the T cells to produce effective immune response. If lack of coordinated stimulus molecules to provide a second signal, will result in T cell reactivity or even induce specific immune tolerance cells into apoptosis.B7- H1, B7- H3 and B7- H4 is subsequently found three new members of the family of B7, respectively and expression in the activation of T cell receptor interactions, mediated negative signal regulating T cell activation and proliferation.Immune stimulation total molecules B7- H1(B7 homolog 1) also called PD- L1(Programmed death- ligand 1) or CD274, it was proved to be apoptosis molecule- 1(Programmed death 1, PD- 1) ligands.B7- H1 is widely expressed in T cells, B cells, macrophages and dendritic cells, can be in a variety of abnormal expression in tumor tissues. Antigen presenting cell surface molecules B7- H1 can with PD 1 molecules on the surface of the T cells and play a role.B7- H3 from the earliest people DC cDNA cloning B7 family member of the library, belonging to the immunoglobulin family type I transmembrane protein.B7- H3 mRNA widely expressed in human tissue, through immunohistochemical detection method, B7-have been discovered successively in H3 protein expressed in many tumor tissues with high. Coordinate to stimulate the proliferation of CD4 +, CD8 + T cells, increase the CTLs activity, at the same time increase the secretion of IFN- 7 and expression of B7- H3 in tumor cells or the expression level is within the tumor blood vessels and the prognosis of patients with significant negative correlation. Negative stimulus molecule B7- H4 is 2003 years of the new members of the newly discovered B7 family.B7- H4 mRNA expression in normal tissues, and B7- H4 protein little expression in normal tissue.B7- H4 can inhibit CD3 + T cell infiltration, and activate CTL induced apoptosis, and weaken the body’s anti-tumor immune response. At the same time, B7- H4 molecules also can protect the cancer cells evade immune surveillance, provide necessary conditions for the tumor immune escape. Clinical studies have shown that B7- H4 expressed in tumor tissues is closely related to the patients clinical pathological parameters, and high expression of B7-H4 patients prognosis is poorer, often lower survival rate.B7- H1, B7- H3 and B7- H4 in tumor cells and immune cells in the expression of cytokines have been microenvironment, associated with different stages of tumor microenvironment change, may be their specific regulatory mechanism of each are not identical, there may be interaction network. This thesis analyzes the corresponding gastrointestinal tumor occurrence and development stage of microenvironment of B7- H1, B7- H3 and the expression of B7- H4 regular expression, and cell of expression, and then make preliminary discussion on the possible regulatory mechanism. This study to clarify these negative stimulus molecule expressed in colorectal cancer at different stages of tumor immune escape mechanism is of important value of early diagnosis and targeted therapy for colorectal cancer, provide new intervention strategy.The first part: The preoperative and postoperative change of negative costimulatory molecule on peripheral blood in patients with carcinoma of the stomach and colorectumObjective: To study the B7 family member of B7- H1, B7- H3 and B7- H4 preoperative postoperative expression differences in gastrointestinal tract tumor and its clinical significanceMethods: using flow cytometry methods 10 preoperative postoperative peripheral blood in patients with gastric cancer and colorectal cancer in B7- H1, B7- H3 and B7- H4 and the difference between the expression of CD3, CD4, CD8, etcResults:Through the analysis of the preoperative postoperative CD3CD4B7H1 of gastrointestinal cancer patients(P = 3.36 x 10-6), CD3CD4B7H3 P = 0.015;CD3CD8B7H3 CD3CD8B7H1 P = 0.001, P = 0.011 and other four indicators have statistical significance.Suggest they may be in the development of tumor plays a certain role.Conclusion:Current literature reports is less, the meaning of these negative total stimulus molecules increase is not sure, guess these indicators may be associated with maintaining stable, because after the cell itself in response to external stimuli can cause activation, after activation may get some functions, such as secretion of cytokines and other cells.Need to track patients prognosis and for further experiment.The second part: Negative costimulatory molecule expression in colorectal cancerObjective: To test the expression of negative stimulus molecule B7- H1 and B7- H3, analyze their expression and clinical pathological factors and survival time of patients with colorectal cancer, exploring the clinical significance of the expression of B7-H1 and B7-H3;Researches on colorectal cancer microenvironment infiltration of CD8 + and CD68 + cells in the relationship with the prognosis.Methods: 195 cases of colorectal cancer tissue collection, immunohistochemical staining method, analysis of B7- H1 and B7- H3 molecules in cancer and colorectal cancer expression in interstitial tissue, in combination with clinical pathological data of the patients and the survival time, the clinical significance of the statistical analysis of the expression; Immunohistochemical staining method 195 cases of colorectal tumor tissue infiltration of CD8 + and CD68 + cells in relation to prognosis.Results:B7- H1 and B7- H3 molecules in colorectal cancer patients have abnormal high expression, at the same time, has certain correlation with tumor clinical pathology results.B7 molecules- H1 was positively correlated with tumor staging, and negatively correlated with lymph node metastasis of the tumor;B7- H3 and Duke of patients’ s stage and deaths were positively correlated.And it also shows the number of CD8 + T lymphocytes was positively related with the survival of patients.Conclusion:Current literature reports is less, the meaning of these negative total stimulus molecules increase is not sure, guess these indicators may be associated with maintaining stable, because after the cell itself in response to external stimuli can cause activation, after activation may get some functions, such as secretion of cytokines and other cells.Need to track patients prognosis and for further experiment. |
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