| Thyroid cancer is the most common endocrine tumor of human body,and its morbidity is appearing a fleetness increasing in recent years.Despite of the improving therapeutic methods,the overall mortality of thyroid cancer is very low,but its recurrence rate is high.So,it's very essential to find a new diagnosic and prognosic marker for thyroid cancer,research the immunologic mechanism which influences the occurrence,development and prognosis of thyroid cancer,and explore new treatment strategies.Negative co-stimulatory molecule B7-H4 is a new member of the B7 family,which is mainly expressed in some tumor cells,activated T cells,macrophage cells and dendritics cells.It can down-regulate T cell immune response by inhibiting T cell proliferation,cytokine secretion and regulate cell cycle,thus plays an important role in the process of down-regulate anti-tumor immune response.In recent years,with the intenstive study of tumor cell surrounding immunomicroenvironment and tumor immune escape mechanism,we found that B7-H4 could be expressed on several human tumor cells and tumor surrounding infiltration immune cells.As a important part of tumor surrounding immunomicroenvironment,B7-H4 palys an pivotal role in the process of tumor immune escape.It can regulate the biological behavior of tumor cells on the one hand;on the other hand,it contributes to tumorrigenesis and tumor progression by negatively regulate the T cell mediated anti-tumor immunity.In this study,the expression of B7-H4 protein and B7-H4 mRNA,within the number and distribution of tumor infiltrating T lymphocytes(TILs)in thyroid tumor tissues were detected by immunohistochemical stain,reverse transcription-polymerase chain reaction(RT-PCR)and CD3 immunohistochemical stain,thus layed the foundation for the further study of molecular biological mechanism of B7-H4 in the process of tumorigenesis and tumor progression of thyroid cancer.Objective: This thesis aimed to investigate the expression of B7-H4 in human thyroid cancer and determine any association with patient clinicopathological parameters and survival.Methods: B7-H4 expression in 64 clinical thyroid cancer specimens was assessed with immunohistochemistry.Moreover,B7-H4 mRNA expression in 10 fresh resected specimens were evaluated by the reverse transcription-polymerase chain reaction(RT-PCR).Immunohistochemical staining of CD3 was performed to assess the number of tumor infiltrating T lymphocytes(TILs)in thyroid cancer tissues.Results: Positive B7-H4 immunohistochemical staining was observed in 61 out of 64(95.3%)specimens of thyroid cancer tissues.Significantly more B7-H4 mRNA copies were found in thyroid cancer tissues than that adjacent normal tissues.Moreover,B7-H4 expression in human thyroid cancer tissues was significantly correlated with patient TNM stages and extrathyroidal extension(P<0.05),being inversely correlated with the number of TILs(P<0.05).The overall survival rate of the patients with higher B7-H4 expression was significantly worse than that of the patients with lower B7-H4 expression.Conclusions: The expression rate of B7-H4 is higher in thyroid cancer than adjacent normal tissues.This present study suggests that high B7-H4 expression is associated with cancer progression,reduced tumor immunosurveillance and worse patient outcomes in human thyroid cancer.We suggest that B7-H4 should be further investigated as a new diagnostic marker for thyroid cancer,and the blockade of B7-H4 in thyroid cancer would be a strategy to pursue for future immunotherapy in thyroid cancer. |
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