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IL-15 Expression In Human Lung Cancer And Breast Cancer And Its Relationship With Clinical Characters

Posted on:2005-08-25Degree:MasterType:Thesis
Country:ChinaCandidate:W H LiuFull Text:PDF
GTID:2144360125458286Subject:Immunology
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Objective: Interleukin-15,although without sequence homology to Interleukin-2 (IL-2),has the similar biological functional activities with IL-2 such as improving proliferation , differentiation, and cytotoxic function of T,B,and LAK by the shared receptor subunitβandγwith IL-2. This indicates that interleukin- 15 is also a cytokine which is closely associated with immune response. The effective anti-tumor function of IL-2 has already been verified by many experiments. Therefore, IL-15 maybe also have such function. Many researches have found that IL-15 has a relatively wider distribution than IL-2 in vivo. IL-2 is only expressed and secreted by the activated T cells ,while IL-15mRNA has been detecteded in many kinds of tissues (placent , Skeletal muscles ,heart ,spleen ,lung and kidney ,etc) and cells (macrophage, marrow stroma cell, thymus epithelial cells, fetus intestinal endothelial cells, kidney epithelial cells ,etc). Perhaps anti-tumor function of IL-15 might be much wider than IL-2 in vivo. Recently, some studies showed that IL-15mRNA was found in some kinds of tumor cells, but the secretion of IL-15 is quite low and cant even be detected sometimes. When the tumor cell lines of lung cancer or breast cancer highly secreting IL-15 constructed by gene engineering techonology, were injected into the nude mice, they were rejected completely .When the nude mice were rechallenged with the wide type tumor cells, the same result was found . One of the important mechanism of rejection may be that Il-15 highly secreted by the transfected tumor cells stimulate a great deal of NK to infiltrate into tumor and kill tumor cells. This strongly showed that IL-15 may be an effective immune theroputic cytokine to lung cancer and breast cancer.Because the nude mice don't have thymus ,they are lack of major immune cells of αβ+ T whose differentiation and maturation depend on thymus. Therefore it is yet unkown that the same result in man as in the nude mice exist or not. In addition, some experiments showed that in ATL and CTCL, IL-15 binded its own IL-15Rαand stimulated its own growth in an autocrine manner . So it is quite necessary to do some researches directly in human tumor to find the relationship between IL-15 expression and clinical characters.The present study was to measure IL-15 and IL-15R αexpression and to detect infiltrating NK and CD8+ cells in human lung cancer and breast cancer. We aimed at making clear the effect of IL-15 on the development of human lung cancer and breast cancer to supply the experimental evidence for properly using IL-15 in anti-tumor immunotherapy. Methods: IL-15, IL-15Rα, NK cells and CD8+cells were studied with immunohistochemical staining in 29 cases of lung cancer (11 cases in the first stage, 10 cases in the second stage, 8 cases in the third stage) and 51 cases of breast cancer (7cases in the first stage, 22 cases in the second stage, 15 cases in the third stage, 7 cases in the fourth stage). Positive-staining density(PSD) of IL-15 and IL-15Rα was assessed by an automatic image analyzer.The positive cell density (PCD) was mean value of CD57+ or CD8+ cells in 5 random fields under microscope. The data were shown by x±s. The correlation between the existence of IL-15 ,IL-15Rα, NK cells and CD8+ cells in tumor and the clinical characters was analysed. ResultsImmunohistochemical staining: positive staining was yellow ,yellow-brown and brown with the increasing of target protein.1.1 IL-15 stainingThere were IL-15 positive staining in 29 cases of lung cancer and 46 of breast cancer. Five cases of breast caner were negative. In positive cases most tumor cells and some infiltrating lymphocytes were stained. The staining was mainly on the cell surface and in the cytoplasm. The nuclear was not stained. In cases of the early stage, positive-staining tumor cells were more and the staining was intense. In cases of the late stage positive-staining tumor cells are less and the staining was weak. PSD in 29 cases of lung cancer was 1179.887±658.
Keywords/Search Tags:IL-15, IL-15 Rα, NK, CD8, immunohistochemistry, lung cancer, breast cancer
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