Study Of The Correlation Between Immune Cells And Tumor Angiogenesis In Breast Carcinoma Microenvironment

Objective The tumor microenvironment is constituted by tumorcells stroma and microvasculars. The stroma includes: mesenchymalcells, immunocyte, blood vessels and lymphatic vessels, etc. Thecomposition of the tumor microenvironment plays an essential role inthe process of destruction of normal tissue such as tumor growth,invasion and metastasis. Growth and spread of tumors are a result of theinteraction between tumor cells and stroma. The local part of body’sreaction on tumor can be directly reflected by the tumor immunemicroenvironment，particularly the cell-mediated immune. It is reportedthat in malignant tumor microenvironment, the immunocytes and theirsecreted factors participate in the adjustment of tumor growth andinvasion, and there is interaction between the immunocyte in themalignant tumor microenvironment and stroma angiogenesis. So far, aresearch about comprehensive analysis of the interactions betweentumor cells, lymphocytes infiltrating tumor and neovascularization instroma not yet has been explicitly reported. Human breast cancer tissuespecimens were used in the experiments. Immunohistochemical methodwas used to detect the type and quantity of immune cells in themicroenvironment of breast cancer tissue, and to analyze the relationships between tumor and angiogenesis. Aimed at clarifying:(1)the infiltration rate of CD4+and CD8+T lymphocyte in the breastcancer microenvironment, to clear its tips significance in breast cancerincidence and progression and to lay the foundation for further analysisof its activity and subtypes;(2) the role of CTLA-4in the process ofbreast cancer immune escape, to detect CTLA-4expression in breastcancer tissue and its interstitial lymphocytes;(3) a morphological basisfor further study of stroma immune cells and angiogenesis regulatorynetworks, to analysis the relationship between CD4+and CD8+Tlymphocytes and stroma microvascular density, as well as thecorrelation between CTLA-4and VEGFR2expression.Results(1)CD4and CD8molecules expression in T-cells of breast cancerand adjacent breast tissue.CD4expression level is lower than the adjacent tissues in breastinvasive ductal carcinoma with statistically significant difference(P<0.05). There is a statistically significant difference between theexpression of CD4in various levels of breast invasive ductal carcinomatissues (P<0.05). With the reduction in breast cancer histological level,the expression of CD4gradually reduce.CD8expression level is higher than the adjacent tissues in breastinvasive ductal carcinoma without statistically significant difference (P>0.05). There is a statistically significant difference between theexpression of CD8in various levels of breast invasive ductal carcinomatissues (P<0.01). With the reduction in breast cancer histological level,the expression of CD8gradually increased.CD4and CD8expression rate ratio in the adjacent tissues and invasiveductal carcinoma tissues were3.24±1.02and2.16±2.17, no statisticallysignificant difference between them (P>0.05). There is a statisticallysignificant difference in each breast cancer histological levels (P <0.01).Microvessel density(MVD)has been detected with CD34signed stromamicrovascular endothelial cells. The MVD of breast invasive ductalcarcinoma tissues is obviously higher than the MVD of adjacent tissues,and indicates an increasing trend, while breast cancer histological levelreduced. The correlation analysis showed that MVD value was negativecorrelation with the CD4as well as CD4and CD8expression rate ratio,and positive correlation with CD8(P<0.01).(2)CTLA-4and VEGFR2expression in breast cancer.CTLA-4expression both in T cells of breast stroma and tumor cells.Between adjacent tissues and interstitial there no significant differencein stroma. With the degree of malignancy, while positive rate alsoincreased, there is a significant difference (P<0.05). Its expression oftumor has a significant difference compared to the adjacent tissues(P<0.05). While the degree of malignancy increased, the expression rate also increased, there is a significant difference (P<0.05).VEGFR2expressed on the cytoplasm and membrane of cancer cells.Compared with cancer and adjacent tissues, there is no significantdifference (P>0.05). While the degree of malignancy increased, theexpression rate also increased, there is a significant difference (P<0.05).The expression of CTLA-4in tumor tissues was positively correlatedwith the expression of VEGFR2in tumor tissues (R=0.148, P=0.005).Conclusion In breast cancer,the expression of CD4decreased, andCD8expression elevated, CD4/CD8ratio decreased, This results suggestthat T cells in the breast cancer microenvironment areimmunosuppressed. CTLA-4expression was detected both in breastcancer parenchyma and interstitial, the higher the degree of infiltration,the more obvious of expression, proving that it`s a negative regulatoryfactor. The expressions of CTLA-4and VEGFR2in breast cancer havepositive correlation. The morphological evidences provide for thefurther study of the tumor microenvironment as a target for combinationtherapy treatment of malignant tumors.