| Objective: Iit is presumede that the development of tumors is related to a defect of a host immunosurveillance system and an escape mechanism of tumors from host immune responses. The adaptive immunity in human being include humoral immunity and cell immunity, and the cell immunity mediated by T cells plays a crucial role in tumor immunosurveillance. T cells are significant immune competent cell, and according to the CD molecule on cellular membrane, T cells can be divided into CD4+T and CD8+T cells. CD4+T cells play central roles in regulation of the immune system in mammals, and CD4+T cells include distinct effector lineages, Th1, Th2 and Treg, each characterized by the production of a unique profile of effector cytokines. A new subset of CD4+ T cells, termed Th17 cells, has been characterized by the prodution of IL-17 in 2005. The primary function of Th17 cells is to fight infection by bacterial and fungal pathogens, and Th17 cells are also involved in inflammation and autoimmune disease. Recently, more and more research has shown that Th17 cells are found in both mouse and human tumors. However, the biologic role of Th17 cells is poorly understood in the tumor microenvironment.Breast carcinoma is a lethal malignant tumor, and in the first place of the serious diseases threatening female's health in developed country and some big cities of our country. At present, operation, chemothreapy and radiotherapy are the main methods to treat tumors, while all have some limitations. In order to enhance the therapeutic efficacy of breast carcinoma, usually employ the combined therapy of the three main methods by turns. But the five year survival rate of breast carcinoma patient still is not satisfactory. It is the day to look for the better methods to treat breast carcinoma.Immunotherapy of tumors which can not only enhance the immune function of host, kill tumor cells in specific way, but also has less side-effects on normal tissues and more and more people have pay attention to immunotherapy. In order to investigate the possibility that if Th17 cells can be used as an new therpeutic target of breast carcinoma, in this study, we examined the express rate of Th17 cells in the cancer tissue and non-cancerous tissue of patients with invasive breast carcinoma, and determined if the express rate of Th17 cells in tumor tissues contribute to influence the clinical pathology factors of the homologous patients. In order to research the antitumor activity, relate mechanisms and provided basis for clinical application of Th17 cells, we study further the effects of Th17 cells in animal model.Methods:1 Expression of Th17 cells and Treg cells in the breast cancer tissues and non-cancerous tissues were detected by flow cytometry (FCM) in 30 breast carcinoma patients, and their correlation with clinical pathology factors was statistical analyzed by multiple linear regression analysis.The expression of interleukin-17 (IL-17), interleukin-1β(IL-1β), interleukin-6 (IL-6), transforming growth factor-β(TGF-β) and interleukin-10 (IL-10) in the breast cancer tissues were measured by immunohistochemical staining, and their correlation with the expression of Th17 cells or Treg cells were statistical analyzed by linear correlation dependablity analysis.2 The CD4+CD62L+ T cells purified by MACS were stimulated under different cytokine conditions to induce and amplify mice Th17 cells in vitro. At the 0, 7 or 12 day after mice were injected with tumor cells, the Th17 cells (experiment group) or PBS (control group) was infused through tumor adjacent into tumor barring mice. The tumor changing and the survival curves of tumor model were detected.3 4T1/IL-17, 4T1/pcDNA3.1 and the parental 4T1 cells were respectively inoculated to mice in the subcutaneous tissue. Three mice of every group were killed on the six weeks after tumor cells inoculation, the tumors were obtained from mice. The other mice of every group were used to observe survival and tumor size. FCM, real time PCR and Western blot were used to determine IL-17 protein expression and Th17 cells ratio in tumor tissues to explain the anti-tumor effect of 4T1/IL-17 cells.Results:1 Compared with the non-cancerous breast tissues, there are significant augment of Th17 cells in the malignant breast tissues, and the Th17 cells display anti-tumor effect in human breast cancer.2 Th17 cells skewing depend on the locally cytokines microenviroment in human breast cancer tissues.3 Compared with the non-cancerous breast tissues, there are significant augment of Treg cells in the malignant breast tissues, and the IL-10 secreted by Treg cells may involve in their promote-tumor effect.4 In human breast cancer tissues, the ratio of Th17 cells has nothing with the ratio of Treg cells.5 Ascertain the best cytokine combination inducing the mice Th17 cells from CD4+CD62L+ T cells in vitro.6 Adoptive transfer of Th17 cells cultured in vitro through tumor adjacent into tumor barring mice, the tumors of mice had accepted Th17 cells adoptive immunotherapy developed obviously slower than the mice had not. And the survival time of tumor barring mice had accepted Th17 cells adoptive immunotherapy also was more longer than the tumor barring mice had not.7 IL-17 secreted from 4T1/IL-17 cells can induce the express of TGF-βand IL-6, this cytokines microenviroment can benefit the skew of Th17 cells.8 The accrescence of Th17 cells in tumor tissues can promote the tumor infiltration and function of CTL, and this may involve in the anti-tumor effect of Th17 cells.Conclusion: There are significant augment of Th17 cells in the malignant breast tissues compared with the non-cancerous breast tissues. And the increased Th17 cells in the tumor tissue of breast cancer patients display anti-tumor effect.To augment the cells population of Th17 cells in the breast tumor tissues by adoptive immunotherapy or altering the cytokine microenvironment in breast tumor tissues may be the novel immunotherapy method of breast carcinoma.
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