本文選題：Tfh細(xì)胞 + Tfr細(xì)胞��； 參考：《河北醫(yī)科大學(xué)》2015年碩士論文

【摘要】：背景:結(jié)直腸癌是全世界發(fā)病率排名第三的惡性腫瘤,每年有超過(guò)100萬(wàn)患者確診為結(jié)直腸癌。傳統(tǒng)治療手段(手術(shù),化療,放療,靶向治療)療效不理想。除了腫瘤本身的機(jī)制外,腫瘤微環(huán)境特別是炎癥反應(yīng)、免疫反應(yīng)與腫瘤的進(jìn)展甚至放化療、靶向藥物抵抗有關(guān)�？梢哉f(shuō),腫瘤免疫治療的時(shí)代已經(jīng)到來(lái)。事實(shí)上越來(lái)越多的證據(jù)表明,在預(yù)防腫瘤的發(fā)生、生長(zhǎng)和轉(zhuǎn)移擴(kuò)散中免疫系統(tǒng)扮演重要的角色。對(duì)于CD4+T淋巴細(xì)胞亞群的研究是近年來(lái)免疫學(xué)研究的一個(gè)熱點(diǎn)。Tfh作為CD4+T淋巴細(xì)胞亞群的一種,是近年來(lái)研究發(fā)現(xiàn)的一種特殊的輔助性T細(xì)胞,表達(dá)CXCR5的Tfh細(xì)胞在CXCL13的趨化下,被募集到淋巴濾泡,參與誘導(dǎo)B細(xì)胞的分化及生發(fā)中心的形成,通過(guò)產(chǎn)生IL-21等細(xì)胞因子以及表達(dá)ICOS等粘附分子來(lái)調(diào)節(jié)機(jī)體的免疫功能。而Tfr細(xì)胞作為Tfh細(xì)胞的調(diào)節(jié)對(duì)應(yīng)物,兼有Tfh和Foxp3+Treg細(xì)胞的表型特征,抑制生發(fā)中心的形成及B細(xì)胞的分化,充當(dāng)與Tfh相反的角色。近來(lái)研究表明失調(diào)的免疫系統(tǒng)在乳腺癌、非小細(xì)胞肺癌和肉瘤的發(fā)生中扮演重要的作用。而關(guān)于Tfh和Tfr在結(jié)直腸癌患者中表達(dá)的研究,國(guó)內(nèi)外尚少有報(bào)道。本研究分別采用流式細(xì)胞術(shù)和酶聯(lián)免疫吸附實(shí)驗(yàn)檢測(cè)結(jié)直腸癌患者和健康人外周血Tfh、Tfr的表達(dá)和上清IL-21的含量,并分析其與臨床病理參數(shù)的關(guān)系,探討其在結(jié)直腸癌中表達(dá)的意義。目的:檢測(cè)Tfh和Tfr在結(jié)直腸癌患者和健康對(duì)照組人外周血表達(dá)水平,同時(shí)測(cè)定外周血上清IL-21含量。分析Tfh和Tfr與臨床病理參數(shù)的關(guān)系,探討其在結(jié)直腸癌中表達(dá)的意義。方法:1通過(guò)流式細(xì)胞術(shù)檢測(cè)實(shí)驗(yàn)組結(jié)直腸癌患者和健康對(duì)照組人外周血中CD4+CXCR5+PD-1+Foxp3-Tfh細(xì)胞和CD4+CXCR5+PD-1+Foxp3+Tfr細(xì)胞的表達(dá)。2用酶聯(lián)免疫吸附試驗(yàn)(ELISA)方法,在分子水平檢測(cè)實(shí)驗(yàn)組結(jié)直腸癌患者和健康對(duì)照組人外周血上清IL-21含量。結(jié)果:1研究對(duì)象的一般信息和臨床特點(diǎn)實(shí)驗(yàn)組結(jié)直腸癌患者共62例,男性34例,女性28例,年齡范圍23~83歲,平均年齡57.6歲,中位年齡58.5歲,病理均證實(shí)為腺癌。TNM分期:Ⅰ期7例,Ⅱ期21例,Ⅲ期25例,Ⅳ期9例(肝轉(zhuǎn)移4例,肺轉(zhuǎn)移3例,腹腔廣泛轉(zhuǎn)移1例,腦轉(zhuǎn)移1例),其中Ⅰ、Ⅱ、Ⅲ及部分Ⅳ期(4例肝轉(zhuǎn)移)患者均行手術(shù)治療。有淋巴結(jié)轉(zhuǎn)移的32例,無(wú)淋巴結(jié)轉(zhuǎn)移的30例。健康對(duì)照組共30例,男性6例,女性24例,年齡范圍26~78歲,平均年齡53.2歲,中位年齡54歲。實(shí)驗(yàn)組與健康對(duì)照組在年齡、性別、吸煙狀態(tài)等方面相比沒(méi)有統(tǒng)計(jì)學(xué)差異。2實(shí)驗(yàn)組和對(duì)照組外周血中Tfh細(xì)胞和Tfr細(xì)胞的表達(dá)以CD4+CXCR5+PD-1+Foxp3-作為Tfh細(xì)胞的標(biāo)記,CD4+CXCR5+PD-1+Foxp3+作為Tfr細(xì)胞的標(biāo)記。通過(guò)流式細(xì)胞術(shù)檢測(cè)實(shí)驗(yàn)組結(jié)直腸癌患者和對(duì)照組健康人外周血中Tfh細(xì)胞和Tfr細(xì)胞的表達(dá)。P1門為外周血淋巴細(xì)胞,設(shè)CD4+T細(xì)胞為2門,Q3和Q4分別為外周血中Tfh細(xì)胞和Tfr細(xì)胞的表達(dá)情況。3實(shí)驗(yàn)組和對(duì)照組人外周血Tfh細(xì)胞和Tfr細(xì)胞的表達(dá)實(shí)驗(yàn)組CRC患者外周血Tfh細(xì)胞占CD4+T細(xì)胞的百分比高于健康對(duì)照組(2.93±2.48vs2.09±1.34,P=0.038);而實(shí)驗(yàn)組CRC患者外周血Tfr細(xì)胞低于健康對(duì)照組(0.16±0.09vs0.2±0.11,P=0.047)。4結(jié)直腸癌患者外周血Tfh細(xì)胞與臨床病理參數(shù)的關(guān)系有淋巴結(jié)轉(zhuǎn)移者Tfh細(xì)胞占CD4+T細(xì)胞百分比較無(wú)淋巴結(jié)轉(zhuǎn)移者高(2.85±1.5 vs2.20±1.2)。各TNM分期間Tfh細(xì)胞占CD4+T細(xì)胞百分比相比較,Ⅰ期(1.39±0.64)和Ⅳ期(1.97±0.82)相比較,P=0.04,有統(tǒng)計(jì)學(xué)差異;而Ⅰ期和Ⅱ期、Ⅲ期相比較及Ⅱ期、Ⅲ期、Ⅳ期間相互比較P值均大于0.05,沒(méi)有統(tǒng)計(jì)學(xué)差異。比較CRC患者CEA5ng/ml和CEA5ng/ml兩組間Tfh細(xì)胞表達(dá)(3.06±2.79vs2.19±2.16,P=0.173),無(wú)統(tǒng)計(jì)學(xué)差異。5酶聯(lián)免疫吸附實(shí)驗(yàn)檢測(cè)實(shí)驗(yàn)組結(jié)直腸癌患者和健康對(duì)照組外周血上清IL-21水平,結(jié)果顯示:實(shí)驗(yàn)組結(jié)直腸癌患者血清IL-21水平高于健康對(duì)照組(196.48±69.85vs149.85±91.49,P0.05)。結(jié)論:1結(jié)直腸癌患者外周血中Tfh細(xì)胞表達(dá)量升高,同時(shí)伴有Tfr表達(dá)量下降,且外周血上清IL-21水平升高。2 Tfh、Tfr細(xì)胞可能參與了結(jié)直腸癌進(jìn)展。
[Abstract]:Background: colorectal cancer is the third most malignant tumor in the world. More than 1 million patients are diagnosed with colorectal cancer every year. Traditional treatments (surgery, chemotherapy, radiotherapy, targeted therapy) are not effective. In addition to the mechanism of the tumor itself, the tumor microenvironment especially the inflammatory reaction, the immune response and the progression of tumor and even radiotherapy and chemotherapy. The age of tumor immunotherapy has come. In fact, more and more evidence suggests that the immune system plays an important role in the prevention of tumor occurrence, growth and metastasis, and the study of CD4+T lymphocyte subsets is a hot spot in immunological research in recent years as a CD4+T lymph node. A kind of cell subgroup is a special kind of auxiliary T cell found in recent years. The Tfh cells expressing CXCR5 are recruited into the lymphoid follicles in the chemotactic of CXCL13, participate in the differentiation of B cells and the formation of the germinal center, and regulate the immune function by producing IL-21 and other adhesion molecules such as ICOS and other cytokines. Tfr cells, as a regulatory counterpart of Tfh cells, also have phenotypic characteristics of Tfh and Foxp3+Treg cells, inhibit the formation of germinal centers and differentiate between B cells, and act as opposite roles to Tfh. Recent studies have shown that the dysfunctional immune system plays an important role in the development of breast cancer, non small cell lung cancer and sarcomas, while Tfh and Tfr are in place. The study of colorectal cancer patients was rarely reported at home and abroad. Flow cytometry and enzyme-linked immunosorbent assay were used to detect the expression of Tfh, Tfr and the content of IL-21 in the peripheral blood of colorectal cancer patients and healthy people, and to analyze the correlation with the clinicopathological parameters and to explore the significance of their expression in colorectal cancer. To detect the level of peripheral blood expression of Tfh and Tfr in colorectal cancer patients and healthy controls, and to determine the IL-21 content of the peripheral blood supernatant, and to analyze the relationship between Tfh and Tfr and the clinicopathological parameters and to explore the significance of their expression in colorectal cancer. Methods: 1 the flow cytometry was used to detect the colorectal cancer patients and the healthy control group. The expression of CD4+CXCR5+PD-1+Foxp3-Tfh and CD4+CXCR5+PD-1+Foxp3+Tfr cells in peripheral blood.2 by enzyme linked immunosorbent assay (ELISA) method, at the molecular level, the content of IL-21 in the peripheral blood supernatant of colorectal cancer patients and healthy controls was detected at the molecular level. Results: 1 of the experimental group of colorectal cancer patients with the same information and clinical characteristics A total of 62 cases, 34 male and 28 female, age range 23~83 years, average age 57.6 years, middle age 58.5 years old, pathology confirmed.TNM staging of adenocarcinoma: stage I, 21 cases, stage III 25 cases, stage IV 9 cases (4 cases of liver metastasis, 3 lung metastasis, peritoneal metastasis 1, 1 cases of brain metastasis), of which, I, II, III and part IV stage (4 case of liver metastases) There were 32 cases of lymph node metastasis and 30 cases without lymph node metastasis. The healthy control group was 30 cases, 6 men and 24 women, the age range was 26~78 years, the average age was 53.2 years and the median age was 54 years. The experimental group and the healthy control group had no statistical difference between the.2 experiment group and the control group at the age, sex, and smoking status. The expression of Tfh and Tfr cells in the blood was marked by CD4+CXCR5+PD-1+Foxp3- as a Tfh cell, and CD4+CXCR5+PD-1+Foxp3+ as a marker for Tfr cells. The expression of Tfh cells and Tfr cells in peripheral blood of the colorectal cancer patients and the control group was detected by flow cytometry. The.P1 gate of the peripheral blood of the peripheral blood was 2 of the peripheral blood lymphocytes, and the CD4+T cells were set up to be 2. The expression of Tfh and Tfr cells in peripheral blood, Q3 and Q4, respectively,.3 experimental group and control group, the expression of Tfh cells and Tfr cells in the peripheral blood of the control group, the percentage of Tfh cells in the peripheral blood of CRC patients was higher than that of the healthy control group (2.93 + 1.34, P=0.038), and the peripheral blood of the experimental group was lower than the healthy control group. The relationship between the peripheral blood Tfh cells and the clinicopathological parameters in the patients with.4 colorectal cancer (0.16 + 0.09vs0.2 + 0.11, P=0.047) with lymph node metastasis, Tfh cells accounted for the percentage of CD4+T cells with no lymph node metastasis (2.85 + 1.5 vs2.20 + 1.2). The percentage of Tfh cells in TNM staging was compared with the percentage of CD4 +T cells, stage I (1.39 + 0.64) and IV stage (1.97 + 0.82) compared, P=0.04, there were statistical differences, while phase I and stage II, phase II, stage II, stage III and IV were more than 0.05, and there was no statistical difference. Tfh cells in CEA5ng/ml and CEA5ng/ml two groups of CRC patients were compared with Tfh cells (3.06 + 2.79vs2.19 + 2.16, P=0.173), and there was no statistical difference in the.5 enzyme immunoadsorption experiment The IL-21 level of peripheral blood supernatant in the experimental group and the healthy control group was detected. The results showed that the serum IL-21 level of the colorectal cancer patients in the experimental group was higher than that of the healthy control group (196.48 + 69.85vs149.85 + 91.49, P0.05). Conclusion: the amount of Tfh cells in the peripheral blood of 1 colorectal cancer patients was increased, and the expression of Tfr was decreased, and the peripheral blood was in the peripheral blood. Supernatant IL-21 level increased.2 Tfh, Tfr cells may participate in the progression of colorectal cancer.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R735.34

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 王漢濤 ,Kraemer M.;隨訪危險(xiǎn)因素分析:復(fù)發(fā)和非復(fù)發(fā)結(jié)直腸癌的比較[J];中國(guó)實(shí)用外科雜志;2001年12期

2 蘇森;患結(jié)直腸癌婦女后代癌癥的危險(xiǎn)性增加[J];中國(guó)腫瘤;2001年06期

3 汪一虹;在確定的法國(guó)人群中年齡<45歲結(jié)直腸癌病人與≥45歲結(jié)直腸癌病人的比較[J];國(guó)外醫(yī)學(xué)(消化系疾病分冊(cè));2002年01期

4 李會(huì)晨;結(jié)直腸癌解剖位置的連續(xù)性右向遷移[J];國(guó)外醫(yī)學(xué).外科學(xué)分冊(cè);2003年03期

5 李志霞;結(jié)直腸癌復(fù)發(fā)及轉(zhuǎn)移的綜合治療[J];中華胃腸外科雜志;2003年06期

6 何建苗,蒲永東,曹志宇,劉衛(wèi)平;老年人結(jié)直腸癌186例的外科治療[J];中華胃腸外科雜志;2003年05期

7 保紅平,方登華,高瑞崗,李奎,張雪松,劉天錫;青年人結(jié)直腸癌臨床病理分析[J];中國(guó)普外基礎(chǔ)與臨床雜志;2004年01期

8 章江;;監(jiān)測(cè)結(jié)直腸癌非常必要[J];國(guó)外醫(yī)學(xué)情報(bào);2004年04期

9 郜文秀,楊艷芳,梁小波,李耀平,李佩珍;細(xì)胞粘附分子變異體在結(jié)直腸癌中的表達(dá)及預(yù)后[J];中國(guó)公共衛(wèi)生;2005年07期

10 Nozawa T. ,Enomoto T. ,Koshida Y. ,M. Kuranami,王志宇;人結(jié)直腸癌黏膜下血小板源性內(nèi)皮細(xì)胞生長(zhǎng)因子特異性增強(qiáng)表達(dá)[J];世界核心醫(yī)學(xué)期刊文摘(胃腸病學(xué)分冊(cè));2005年06期

相關(guān)會(huì)議論文 前10條

1 鄭樹(shù);;結(jié)直腸癌預(yù)后與轉(zhuǎn)移相關(guān)因素分析[A];2005年浙江省腫瘤學(xué)術(shù)會(huì)議全國(guó)大腸癌轉(zhuǎn)移與復(fù)發(fā)的診治研討會(huì)學(xué)術(shù)論文集[C];2005年

2 鄒一峰;吳小劍;蘭平;;結(jié)直腸癌免疫治療新進(jìn)展[A];第十一次全國(guó)中西醫(yī)結(jié)合大腸肛門病學(xué)術(shù)會(huì)議論文匯編[C];2006年

3 郁寶銘;;結(jié)直腸癌治療的進(jìn)展及其新理念[A];2006年浙江省肛腸外科學(xué)術(shù)年會(huì)論文匯編[C];2006年

4 王錫山;;結(jié)直腸癌治療的困惑之我見(jiàn)[A];第九屆全國(guó)腫瘤轉(zhuǎn)移學(xué)術(shù)大會(huì)暨2011年黑龍江省醫(yī)學(xué)會(huì)腫瘤學(xué)年會(huì)報(bào)告集[C];2011年

5 秦建平;;未病思想中的結(jié)直腸癌預(yù)防[A];貴州省中西醫(yī)結(jié)合學(xué)會(huì)肛腸學(xué)會(huì)第五屆學(xué)術(shù)交流會(huì)暨新技術(shù)新進(jìn)展學(xué)習(xí)班論文匯編[C];2012年

6 高文慶;陳會(huì)林;童蕾;陸松春;;老年梗阻性結(jié)直腸癌診療體會(huì)(附42例報(bào)告)[A];首屆“之江中醫(yī)藥論壇”暨浙江省中醫(yī)藥學(xué)會(huì)2011年學(xué)術(shù)年會(huì)論文集[C];2011年

7 王啟遠(yuǎn);周長(zhǎng)江;高云飛;徐巖;李坤;;血管內(nèi)皮生長(zhǎng)因子與結(jié)直腸癌[A];《中華急診醫(yī)學(xué)雜志》第八屆組稿會(huì)暨急診醫(yī)學(xué)首屆青年論壇論文匯編[C];2009年

8 巴一;;結(jié)直腸癌靶向治療進(jìn)展[A];第三屆中國(guó)腫瘤內(nèi)科大會(huì)教育集暨論文集[C];2009年

9 何超;朱洪波;;結(jié)直腸癌的生物治療[A];2009年浙江省腫瘤外科學(xué)術(shù)年會(huì)暨腫瘤外科規(guī)范化診治學(xué)習(xí)班論文匯編[C];2009年

10 萬(wàn)德森;;進(jìn)一步提高結(jié)直腸癌療效的思考[A];2009年浙江省腫瘤學(xué)術(shù)年會(huì)暨腫瘤診治新進(jìn)展學(xué)習(xí)班論文匯編[C];2009年

相關(guān)重要報(bào)紙文章 前10條

1 中華醫(yī)學(xué)會(huì)腫瘤學(xué)分會(huì)主任委員 顧晉;分期不精確 致結(jié)直腸癌過(guò)度治療[N];健康報(bào);2012年

2 本報(bào)記者 賈巖;跨線治療成結(jié)直腸癌最后防線[N];醫(yī)藥經(jīng)濟(jì)報(bào);2012年

3 本報(bào)記者 賈巖;跨線治療構(gòu)筑結(jié)直腸癌最后防線[N];醫(yī)藥經(jīng)濟(jì)報(bào);2012年

4 本報(bào)記者 林琳;結(jié)直腸癌：可以治愈的癌癥[N];醫(yī)藥經(jīng)濟(jì)報(bào);2013年

5 記者 張妍　通訊員 熊靜帆 朱品磊;深圳結(jié)直腸癌發(fā)病高于全國(guó)[N];深圳商報(bào);2013年

6 本報(bào)記者 孫剛;預(yù)防結(jié)直腸癌：請(qǐng)管住嘴[N];解放日?qǐng)?bào);2013年

7 上海市中醫(yī)醫(yī)院腫瘤科 侯鳳剛 副主任醫(yī)師;中醫(yī)藥在結(jié)直腸癌治療中的作用和特色[N];上海中醫(yī)藥報(bào);2014年

8 李華虹 孫瑜淼 記者 李麗云 實(shí)習(xí)生 陰浩;專家呼吁：結(jié)直腸癌應(yīng)多學(xué)科規(guī)范化診療[N];科技日?qǐng)?bào);2014年

9 ;降低結(jié)直腸癌復(fù)發(fā)有新療法[N];人民日?qǐng)?bào);2003年

10 韓自力;新化療方案可高效治療結(jié)直腸癌[N];健康報(bào);2007年

相關(guān)博士學(xué)位論文 前10條

1 陳濤;MicroRNA-31/FIH-1調(diào)控關(guān)系在結(jié)直腸癌發(fā)生發(fā)展中的作用及其機(jī)制研究[D];復(fù)旦大學(xué);2014年

2 任翡;MYBL2基因在結(jié)直腸癌的表達(dá)及機(jī)制的初步探討[D];復(fù)旦大學(xué);2014年

3 吳朋;結(jié)直腸癌中microRNA-615基因甲基化及其生物學(xué)特性探究[D];復(fù)旦大學(xué);2014年

4 李澤武;MicroRNA-203靶向ZNF217基因調(diào)控結(jié)直腸癌生物學(xué)行為的研究[D];山東大學(xué);2015年

5 徐興遠(yuǎn);低分子肝素對(duì)結(jié)直腸癌患者預(yù)后的影響及相關(guān)機(jī)制的研究[D];復(fù)旦大學(xué);2014年

6 梁洪亮;miR-454在結(jié)直腸癌中的功能及其作用機(jī)制[D];山東大學(xué);2015年

7 金鵬;MMR蛋白在雌激素致結(jié)腸癌細(xì)胞凋亡中的作用及SEPT9檢測(cè)結(jié)直腸癌的研究[D];第三軍醫(yī)大學(xué);2015年

8 珠珠;云南省Lynch綜合征候選基因標(biāo)志物研究[D];昆明醫(yī)科大學(xué);2014年

9 周智航;SEMA3F通過(guò)下調(diào)ASCL2-CXCR4軸而抑制結(jié)直腸癌轉(zhuǎn)移的分子機(jī)制[D];第三軍醫(yī)大學(xué);2015年

10 王林;MiRNA-300對(duì)結(jié)直腸癌腫瘤侵襲和增殖的影響及其調(diào)控機(jī)制的初步研究[D];第三軍醫(yī)大學(xué);2015年

相關(guān)碩士學(xué)位論文 前10條

1 顏斐斐;術(shù)后結(jié)直腸癌患者癌因性疲乏與影響因素的研究[D];南方醫(yī)科大學(xué);2009年

2 李斌;結(jié)直腸癌患者就診延遲分析[D];中南大學(xué);2009年

3 葉建杰;慈溪市結(jié)直腸癌危險(xiǎn)因素病例對(duì)照研究[D];浙江大學(xué);2008年

4 趙波;結(jié)直腸癌危險(xiǎn)因素及臨床流行病學(xué)特征的調(diào)查與分析[D];廣西醫(yī)科大學(xué);2013年

5 宋艷敏;PAQR3基因甲基化水平與結(jié)直腸癌關(guān)系的研究[D];河北大學(xué);2015年

6 黎江;Oct4B1在結(jié)直腸癌干細(xì)胞中的表達(dá)及其與Twist的相關(guān)性研究[D];遵義醫(yī)學(xué)院;2015年

7 楊文婷;PD-L1、SIRT1在結(jié)直腸癌組織中的表達(dá)及意義[D];福建醫(yī)科大學(xué);2015年

8 羅佳;二代測(cè)序分析散發(fā)性結(jié)直腸癌和息肉的基因突變[D];福建醫(yī)科大學(xué);2015年

9 崔慧鵬;精氨酸琥珀酸合成酶（ASS1）高表達(dá)與結(jié)直腸癌惡性進(jìn)展的相關(guān)性研究[D];中國(guó)人民解放軍醫(yī)學(xué)院;2015年

10 崔娟娟;p53和nm23在結(jié)直腸癌中的表達(dá)及其臨床意義[D];河北聯(lián)合大學(xué);2014年

，

本文編號(hào)：2057705