白细胞介素-2对肿瘤引流淋巴结内T细胞亚群作用的研究

发布时间：2018-03-12 10:24

  本文选题：癌症　切入点：乳腺癌　出处：《南京大学》2017年硕士论文　论文类型：学位论文

【摘要】：研究目的:淋巴结转移是癌细胞重要的转移方式之一,同机体淋巴结内免疫功能的下降有着密切的联系。大量研究证实肿瘤引流淋巴结内的免疫细胞特别是T细胞会出现数量下降、结构成分改变,进而导致其免疫功能受损。本文通过实验观察对比无淋巴结转移癌症患者引流区淋巴结与有淋巴结转移癌症患者肿瘤引流淋巴结(tumor draining lymph node,TDLN)内T细胞亚群的量,分析其免疫功能的差别,并通过实验研究白细胞介素-2(Interleukin-2,IL-2)对肿瘤引流淋巴结内T细胞亚群的影响,探讨白细胞介素-2成为提高癌症患者淋巴结免疫功能药物的可能性。研究方法:1.我们纳入2016年5月1日-12月31日期间来我院诊治乳腺癌(breast cancer,BC)及甲状腺癌(thyroid cancer,TC)患者,根据术后病理分为对照组及观察组,其中对照组(13例,乳腺癌7例,甲状腺癌6例)为术后病理确诊淋巴结癌转移病人;观察组(13例,乳腺癌6例、甲状腺癌7例)为术后病理确诊无淋巴结癌转移病人。取得患者术中常规清扫淋巴结,采用免疫组化(Immunohistochemistry,IHC)中免疫荧光技术(Immunofluorescence,IF)测定淋巴结内CD3+CD4+T细胞、CD3+CD8+T细胞的量,采用酶联免疫吸附测定法(ELISA法)测定淋巴结内由CD3+CD4+T细胞(Th细胞)分泌的白介素-2、白介素-4(Interleukin-4,IL-4)的浓度。用T检验比较两组CD3+CD4+T细胞、CD3+CD8+T细胞及CD3+CD4+T细胞分泌的IL-2、IL-4的差异,并分析造成两组患者淋巴结免疫功能差异的原因。2.纳入2016年5月1日-12月31日期间来我院诊治乳腺癌及甲状腺癌患者,根据术后病理分为实验A组及实验B组,其中实验A组(11例,乳腺癌6例、甲状腺癌5例)为术前使用白介素-2治疗,术后病理确诊淋巴结癌转移病人;实验B组(11例,乳腺癌4例、甲状腺癌7例)为术前使用白介素-2治疗,术后病理确诊无淋巴结癌转移病人。取得患者术中常规清扫淋巴结,采用免疫组化中免疫荧光技术测定淋巴结内CD3+CD4+T细胞、CD3+CD8+T细胞的量,采用酶联免疫吸附测定法测定淋巴结内由CD3+CD4+T细胞(Th细胞)分泌的IL-2、IL-4的浓度。用T检验比较各组CD3+CD4+T细胞、CD3+CD8+T细胞及CD3+CD4+T细胞分泌的IL-2、IL-4的差异,并分析各组患者淋巴结免疫功能差异的原因,探讨白介素-2成为提高癌症患者淋巴结免疫功能药物的可能性。研究结果:1.观察组淋巴结CD3+CD4+T细胞、CD3+CD8+T细胞及CD3+CD4+T细胞分泌的IL-2、IL-4的测量值均高于对照组,且有统计学意义(P0.05)。2.实验A组淋巴结CD3+CD4+T细胞、CD3+CD8+T细胞及CD3+CD4+T细胞分泌的IL-2、IL-4的测量值均高于对照组,且有统计学意义(P0.05);实验B组淋巴结CD3+CD4+T细胞、CD3+CD8+T细胞及CD3+CD4+T细胞分泌的IL-2、IL-4的测量值均高于观察组,且有统计学意义(P0.05);实验B组淋巴结CD3+CD4+T 细胞、CD3+CD8+T 细胞及 CD3+CD4+T 细胞分泌的 IL-2、IL-4 的测量值均高于实验A组组,且有统计学意义(P0.05)。结论:无淋巴结转移癌症患者其肿瘤引流区内淋巴结的免疫功能明显强于有淋巴结转移癌症患者的肿瘤引流淋巴结,而应用白介素-2后可以明显提升淋巴结内T细胞亚群的量,提高其免疫力从而起到抗肿瘤作用,白介素-2有望成为提高肿瘤引流淋巴结免疫力、辅助癌症治疗的药物。
[Abstract]:Objective: lymph node metastasis is one of the important way of the transfer of cancer cells, with the decline in immune function in lymph nodes are closely linked. A large number of studies have demonstrated that tumor draining lymph nodes in the immune cells, especially T cells will be a decline in the number of components change, thus resulting in impaired immune function. In this paper, through the experiment comparative observation of lymph node metastasis in patients with cancer draining lymph nodes and lymph node metastasis in patients with cancer tumor draining lymph node (tumor draining lymph node, TDLN) in T cell subsets, analyze the immune function difference, and through the experimental study of interleukin -2 (Interleukin-2, IL-2) on tumor draining effect the lymph nodes of T cell subsets, investigate interleukin -2 become the possibility of improving the immune function of drugs in patients with lymph node cancer. Methods: We included 1. -12 month May 1, 2016 31 date To our hospital for diagnosis and treatment of breast cancer (breast, cancer, BC) and thyroid cancer (thyroid cancer, TC) patients, according to postoperative pathology were divided into control group and observation group, the control group (13 cases, 7 cases of breast cancer, 6 cases of thyroid carcinoma) for patients pathologically confirmed lymph node metastasis after operation; the observation group (13 cases, 6 cases of breast cancer, 7 cases of thyroid carcinoma) for pathological diagnosis of lymph node metastasis patients. Routine lymph node dissection in patients, using immunohistochemistry (Immunohistochemistry, IHC) in the immunofluorescence technique (Immunofluorescence, IF) detection of CD3+CD4+T cells in lymph nodes, CD3+CD8+T cells the amount of enzyme linked immunosorbent assay (ELISA) determination of lymph nodes by CD3+CD4+T cells (Th cells) secretion of interleukin -2, interleukin -4 (Interleukin-4, IL-4). The concentration of T test between two groups of CD3+CD4+T cells and secretion of CD3+CD8+T cells and CD3+CD4+T cells in IL-2, IL The differences in -4, and analyze the cause of two groups of patients with lymph node.2. immune function of the difference in the May 1, 2016 -12 month 31 days during our hospital diagnosis and treatment of breast cancer and thyroid cancer patients, according to postoperative pathology were divided into experimental group A and experimental group B, experimental group A (11 cases, 6 cases of thyroid, breast cancer 5 cases of cancer) for interleukin -2 therapy before surgery, patients with pathologically confirmed lymph node metastasis after operation; group B (11 cases, 4 cases of breast cancer, 7 cases of thyroid carcinoma) for interleukin -2 in the treatment of preoperative, postoperative pathological diagnosis of lymph node metastasis patients. Conventional dissection the patient in operation, the immune group of CD3+CD4+T cells in lymph nodes by immunofluorescence technique in CD3+CD8+T cells, the amount of adsorption were determined by CD3+CD4+T cells in lymph nodes by ELISA (Th cells) the secretion of IL-2, the concentration of IL-4. T test groups were compared with CD3+CD4+T cells, CD The secretion of 3+CD8+T cells and CD3+CD4+T cells IL-2, IL-4 difference, and analysis of each group of lymph nodes in patients with immune function difference, investigate interleukin -2 become the possibility of improving the immune function of drugs in patients with lymph node cancer. Results: the observation group of 1. lymph nodes in CD3+CD4+T cells, CD3+CD8+T cells and CD3+CD4+T cells secrete IL-2, IL-4 measurement the value is higher than the control group, and there was statistical significance (P0.05) CD3+CD4+T cells in the experimental group A lymph node.2., secretion of CD3+CD8+T cells and CD3+CD4+T cells IL-2, IL-4 measured values were higher than the control group, and there was statistical significance (P0.05); experimental group B lymph node CD3+CD4+T cells, secretion of CD3+CD8+T cells and CD3+CD4+T cells IL-2 IL-4, the measured values were higher than those in the observation group, and there was statistical significance (P0.05); experimental group B lymph node CD3+CD4+T cells, CD3+CD8+T cells and CD3+CD4+T cells to secrete IL-2, IL-4 The measured values were higher than the experimental group A, and there was statistical significance (P0.05). Conclusion: the lymph node metastasis in patients with cancer of the immune function in tumor draining lymph node was significantly higher in the cancer patients with lymph node metastasis of tumor draining lymph node, and the application of interleukin -2 can significantly enhance the lymph node in T cells the amount of subsets, so as to improve the immunity of antitumor effect of interleukin -2 to improve tumor draining lymph node immunity adjuvant in the treatment of cancer.

【学位授予单位】：南京大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R730.5
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本文编号：1601149