食管癌患者CD4^＋ CD25^＋调节性T细胞的检测及意义

目的：探讨CD4^＋ CD25^＋调节性T细胞在食管癌局部及全身免疫中的作用。方法：流式细胞仪检测97例食管癌患者外周血和20例肿瘤组织的CD4^＋ CD25^＋调节性T细胞比例,比较不同病理类型、不同分期等食管癌患者外周血及肿瘤局部组织的CD4^＋ CD25^＋调节性T细胞的分布变化。结果：食管癌患者肿瘤组织CD4^＋ CD25^＋调节性T细胞比例为（18.97±2.38）%,高于患者外周血比例〔（17.57±3.99）%〕,差异无统计学意义,t=1.511,P〉0.05;食管癌患者肿瘤组织及外周血中CD4^＋ CD25^＋调节性T细胞占CD4＋ T淋巴细胞的比例,均高于同期健康对照组患者外周血的比例（9.35±1.41）%,差异有统计学意义,t值分别为12.111和8.332,P值均〈0.01。CD4^＋ CD25^＋调节性T细胞水平与临床分期（F=9.384）、有无淋巴结转移（t=2.326）有关,P值均〈0.05。结论：食管癌患者全身及肿瘤局部均存在免疫异常,推测CD4^＋ CD25^＋调节性T细胞可能参与了食管癌的发生与发展。     

肺癌患者外周血CD4+CD25+调节性T细胞检测的临床意义

目的:探讨肺癌患者外周血CD4+CD25+调节性T细胞(Treg)的比例变化及其在肿瘤发生发展中的作用.方法:应用流式细胞术检测78例肺癌患者和30例健康者CD4+CD25+Treg比例,分析其与肺癌的临床分期、病理类型、组织学分化程度及手术的关系.结果:肺癌患者外周血CD4+CD25+Treg比例与健康对照组比较,差异有统计学意义,t=2.316,P=0.04.Ⅲ、Ⅳ期肺癌患者Treg比例显著高于Ⅰ+Ⅱ期患者,t值分别为2.205和2.207,P值均为0.04.鳞癌、腺癌、小细胞肺癌高、中和低分化肺癌患者Treg比例显著高于对照组,P<0.05.手术后的肺癌患者Treg比例为(14.38±3.82)%,显著低于手术前的(20.16±5.24)%,t=1.823,P=0.05.结论:肺癌患者外周血CD4+CD25+Treg水平明显升高,且与肺癌的进展密切相关,越晚期水平越高;手朱后肺癌总着外鼠血CD4+CD25+Treg水平明显下调.     

肝癌患者CD4+CD25+调节性T细胞的检测及其临床意义

背景与目的CD4 CD25 调节性T细胞(CD4 CD25 regulatoryTcells)在自身免疫耐受、移植和抗肿瘤应答中起着重要的作用,它们在肿瘤患者中的作用机制尚未阐明。本研究分析、探讨肝癌患者肿瘤组织和外周血CD4 CD25 调节性T细胞频率的临床意义。方法应用流式细胞仪分析肝癌患者的肿瘤组织、外周血和非肝癌对照组中单个核细胞(PBMCs)的CD4 CD25 调节性T细胞频率。结果肝癌患者外周血CD4 CD25 T细胞占PBMCs(6.9±2.8)%,肝癌组织CD4 CD25 T细胞占(6.7±1.6)%,均较对照组显著增高。并且CD4 CD25 T细胞的阳性率与淋巴结转移率和TNM分期存在相关性。淋巴结转移阳性和TNM分期越晚,CD4 CD25 T细胞的阳性率越高。结论CD4 CD25 调节性T细胞在肝癌患者中比例升高,可能是肝癌患者细胞免疫功能削弱的机制之一。     

食管癌患者外周血调节性T细胞亚群格局变化及其临床意义

[目的]分析食管癌患者外周血CD4+CD25+CD127-调节性T细胞(Treg)占CD4+T细胞的比例变化.[方法]采用流式细胞仪检测104例食管癌患者和68例健康及良性疾病对照者外周血中CD4+CD25+CD127-Treg占CD4+T细胞的比例,分析其与临床分期、淋巴结转移及外膜受侵的关系.[结果]食管癌患者与对照组的外周血CD4+CD25+CD127-Treg占CD4+T细胞比例分别为(5.19％±1.82％)和(4.56％±1.16％),两组比较差异有统计学意义(t=2.544,P=0.012).Ⅱa期CD4+CD25+CD 127-Treg细胞比例分别与Ⅱb期和Ⅲa期比较,差异均有统计学意义(P＜0.01);不同年龄、淋巴结及外膜受侵状况患者的外周血CD4+CD25+CD127-Treg细胞比例变化比较无统计学差异(P＞0.05).[结论]食管癌患者外周血CD4+CD25+CD127-Treg占CD4+T细胞的比例明显升高,且分期高患者升高更为明显,提示可能与食管癌免疫逃逸和免疫耐受有关.     

胃癌患者外周血CD4+CD25highCD127low/-调节性T细胞达临床意义分析

目的:研究CD4+ CD25high CD12low/-调节性T细胞(Treg)在胃癌患者外周血中的表达水平,探讨其在肿瘤发病机制及治疗中的作用.方法:采用流式细胞术检测法检测90例胃癌患者(35例为早中期胃癌,55例为晚期胃癌)和3(名健康体检者外周血中CD4+ CD25high CD127low/-Treg的表达水平.结果:90例胃癌患者外周血CD4+T细胞中CD4+CD25highCD127low/-Treg含量为(11.60±5.99)％,高于健康体检者(5.19±1.72)％,t=5.610,P=0.007;Ⅲ+Ⅳ期患者外周血CD4+T细胞中CD4+ CD25high CD127low/-Treg含量为(12.55±6.59)％,明显高于Ⅰ+Ⅱ期患者(10.39±4.68)％(t=4.113,P=0.04)和健康体检者(5.19±1.72)％(t=5.923,P=0.001).手术后胃癌患者CD4+ CD25high CD127low/-Treg水平为(6.12±2.13)％,明显低于手术前(11.25士5.63)％,t=5.237,P=0.04.结论:胃癌患者外周血CD4+ CD25highCD127low/-Treg数量增多且与病程分期相关,手术后Treg数量明显减少,Treg可能参与了胃癌的发生发展.     

大肠癌患者外周血CD4~+ CD25~+ CD127~-调节性T细胞表达及其临床意义

目的:探讨CD4+CD25+CD127-调节性T细胞在大肠癌患者外周血中的表达水平及临床意义。方法:应用流式细胞仪检测200例大肠癌患者外周血CD4+CD25+CD127-调节性T细胞占CD4+T细胞的百分比,并分析其与大肠癌组织的分化程度、淋巴结转移和临床分期的关系。结果:大肠癌患者外周血CD4+CD25+CD127-调节性T细胞占CD4+T细胞的百分率〔(4.84±1.35)%〕明显高于健康对照组〔(0.85±0.25)%〕,差异有统计学意义,P<0.05。低分化者外周血调节性T细胞〔(4.21±0.42)%〕明显高于高分化者〔(3.92±0.41)%〕,差异有统计学意义,P<0.05;有淋巴结转移者外周血调节T细胞〔(4.57±1.44)%〕明显高于无淋巴结转移者〔(2.36±0.68)%〕,差异有统计学意义,P<0.01;Ⅲ和Ⅳ期患者外周血调节性T细胞〔(3.53±1.41)%和(4.38±1.32)%〕明显高于Ⅰ～Ⅱ期〔(1.90±0.86)%〕,差异有统计学意义,P<0.01。结论:大肠癌患者外周血CD4+CD25+CD127调节性T细胞占CD4+T细胞的百分率明显升高,可能在大肠癌的免疫耐受和免...     

胃癌患者外周血CD4+ CD25highCD127low/-调节性T细胞表达临床意义分析

目的:研究CD4+CD25highCD127low/-调节性T细胞(Treg)在胃癌患者外周血中的表达水平,探讨其在肿瘤发病机制及治疗中的作用。方法:采用流式细胞术检测法检测90例胃癌患者(35例为早中期胃癌,55例为晚期胃癌)和30名健康体检者外周血中CD4+CD25highCD127low/-Treg的表达水平。结果:90例胃癌患者外周血CD4+T细胞中CD4+CD25highCD127low/-Treg含量为(11.60±5.99)%,高于健康体检者(5.19±1.72)%,t=5.610,P=0.007;Ⅲ+Ⅳ期患者外周血CD4+T细胞中CD4+CD25high CD127low/-Treg含量为(12.55±6.59)%,明显高于Ⅰ+Ⅱ期患者(10.39±4.68)%(t=4.113,P=0.04)和健康体检者(5.19±1.72)%(t=5.923,P=0.001)。手术后胃癌患者CD4+CD25highCD127low/-Treg水平为(6.12±2.13)%,明显低于手术前(11.25±5.63)%,t=5.237,P=0.04。结论:胃癌患者外周血CD4+CD25highCD127low/-Treg数量增多且与病程分期相关,手术后Treg数量明显减少,Treg可能参与了胃癌的发生发展。     

胃癌患者外周血CD4+CD25+调节性T细胞的检测及其临床意义

目的探讨胃癌患者外周血CD4 CD25 调节性T细胞水平的特点及其临床意义。方法采用流式细胞术检测35例胃癌患者外周血CD4 CD25 调节性T细胞水平并进行分层分析。结果健康对照组CD4 CD25 调节性T细胞水平为(8.69±2.28)%,35例胃癌患者CD4 CD25 调节性T细胞比例为(17.77±8.45)%,统计学有显著差异(P<0.01);进一步分层分析显示随疾病进展外周血CD4 CD25 调节性T细胞水平升高,在III期、IV期尤为明显,统计学有极显著差异(P<0.01)。结论胃癌患者外周血CD4 CD25 调节性T细胞水平的升高与胃癌免疫功能低下及肿瘤的发生发展密切相关,去除这群细胞可有效诱导肿瘤免疫,为肿瘤治疗提供一种新的方法。     

甲状腺乳头状癌患者外周血CD4+CD25+CD127low/-Treg的检测及其临床意义

目的:检测CD4+ CD25+ CD127low/-调节性T细胞(regulatory T cell,Treg)在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)患者外周血的比例,探讨其临床意义。方法:选择2010年8月至2011年2月在上海交通大学医学院附属仁济医院进行手术治疗的PTC患者40例及甲状腺腺瘤患者30例,以CD4+ CD25+ CD127low/-为标志,采用流式细胞术检测PTC患者及甲状腺腺瘤患者外周血中CD4+ CD25+ CD127low/-Treg的比例,分析其与PTC临床病理特征的关系。结果:与甲状腺腺瘤患者比较,PTC患者外周血中CD4+ CD25+ CD127low/- Treg比例明显升高[(7.836±1.668)% vs(5.365±1.156)%,P<0.05];外周血CD4+ CD25+ CD127low/-Treg比例与PTC临床分期、颈部淋巴结转移相关(均P<0.05),与年龄、性别及肿瘤大小无关(P>0.05)。结论:PTC患者外周血CD4+ CD25+ CD127low/-Treg比例显著增加,且与PTC临床分期、颈部淋巴结转移相关。     

CD4+CD25+调节性T细胞在结直肠癌中的表达及其意义

背景与目的:CD4 CD25 调节性T细胞(Treg细胞)是体内自然发生的调节性T细胞的重要亚群,其在体内不仅参与自身免疫性疾病、移植排斥反应等,还在多种恶性肿瘤的发生、发展及免疫治疗中发挥重要作用.本研究探讨CD4 CD25 Treg细胞在结直肠癌中的表达及其意义.方法:收集30例结直肠癌患者的肿瘤组织及远离肿瘤部位组织,用流式细胞术和免疫组织化学方法对肿瘤组织中浸润的CD4 CD25 Treg细胞进行定量及定位分析.结果:CD4 CD25 Treg细胞含量:远离肿瘤部位组织为(5.5±1.3)%,肿瘤组织为(24.1±4.8)%,远离肿瘤部位组织与肿瘤组织相比,差异有显著性(t=5.155,P=0.002);有淋巴结转移者为(27.9±3.6)%,无淋巴结转移者为(20.3±1.3)%,差异有显著性(t=3.489,P=0.025).结论:结直肠癌患者肿瘤组织中浸润的CD4 CD25 Treg细胞的比率显著升高,且与结直肠癌的进展有关.     

CD4+CD25+调节性T细胞与CD4+T、CD8+T细胞在结直肠癌组织中的分布

 目的 分析CD4+CD25+ FOXP3+调节性T细胞（Treg）与CD4+T、CD8+T在结直肠癌（colorectal carcinoma, CRC）组织中的分布及其与临床病理特征之间的关系。方法 收集42例CRC新鲜手术标本,应用冰冻切片、免疫组织化学SP法检测肿瘤组织和癌旁组织中FOXP3+、CD4+T和CD8+T阳性细胞数。结果 CRC患者肿瘤组织中FOXP3表达水平显著升高,与癌旁组织相比差异有统计学意义（P<0.01）;中低分化组Treg细胞数明显高于高分化组（P<0.01）;淋巴结转移组Treg细胞数明显高于无淋巴结转移组（P<0.05）;癌巢内CD4+、CD8+T细胞数及CD4+/CD8+值显著低于间质（P<0.01）;Ⅲ+Ⅳ期、淋巴结转移组癌巢内CD4+/CD8+比值显著低于Ⅰ+Ⅱ期及无淋巴结转移组（P<0.05）;CRC中Treg数量与癌巢内CD4+/CD8+比值显著负相关（r=-0.605, P<0.01）。结论 CRC的发生发展可能与其癌组织局部微环境中Treg数量变化相关,肿瘤局部Treg数量的增多与T淋巴细胞亚群比例失调可能成为肿瘤免疫逃逸的机制之一。     

外周血CD3+、CD4+、CD8+、CD19+水平与喉癌患者预后的相关性

目的 探讨喉癌患者免疫水平的变化与病情进展的关系.方法 选取56例喉癌患者,用流式细胞仪检测不同分组的喉癌患者外周血淋巴细胞和NK细胞的表达水平.结果 手术后患者CD19+显著性下降(P＜0.05),而NK细胞显著上升(P＜0.05);有淋巴结转移的患者比无淋巴结转移的患者NK细胞上升,CD4+下降,二者均有统计学差异(P＜0.05);病理分期中Ⅲ～Ⅳ期的患者比Ⅰ～Ⅱ期表现出CD19+显著性下降(P＜0.05),CD4+则显著上升(P＜0.05).在术后随访18个月中,有复发或转移的患者比无转移且无复发患者CD4+下降,而NK细胞和CD19+上升,均具有统计学差异(P＜0.05).结论 喉癌患者免疫状态和病情之间有一定的联系.     

Immune surveillance: both CD3+ CD4+ and CD3+ CD8+ T cells control in vivo growth of P815 mastocytoma.

The aim of this study was to examine whether a spontaneous immune response controls neoplastic growth in P815-bearing DBA/2 mice, and to characterize the cells involved in tumor resistance in vivo. Several cell lineages such as T-cell-receptor (TcR)-bearing T cells, NK cells and macrophages mediate some anti-tumor activity in vitro. P815 was chosen as a model because it is weakly immunogenic and is a good target both for tumor-specific, MHC-restricted CTL-mediated lysis and for MHC-unrestricted lysis exerted by long-term cultured lymphocytes or activated macrophages. Since most "NK-like activity" in freshly isolated populations appears to be associated with CD3- cells, whereas antigen-specific, MHC-restricted T cells mostly express CD3 determinants, CD3 was a good marker for evaluating the role of T cells and "NK" cells in tumor resistance in vivo. The survival of anti-CD3-treated animals that were inoculated with tumor cells was strongly reduced (mean survival time: 17 days vs. 40 days for the control group) and was associated with increased tumor growth rate. We followed the same approach to define the T-cell subset(s) that mediate(s) this immune response. Both CD4+ and CD8+ T cells were required for induction of immune control on neoplastic growth. The approach used has revealed the important role of CD4+ T cells in immune responses that control in vivo growth of a class-I-positive, class-II-negative tumor and suggests that these cells may play a central role in tumor resistance. Since CD4+ cells are activated by soluble, exogenous proteins, this finding may have important implications for immunotherapy.     

Epithelial mesenchymal transition correlates with CD24+CD44+ and CD133+ cells in pancreatic cancer

The epithelial-mesenchymal transition (EMT) has been linked to induction of a stem-cell like phenotype, characterized by altered cell surface marker expression and increased tumor formation. The aim of this study was to investigate whether EMT correlates with CD24+CD44+ and CD133+ cells in pancreatic cancer. The morphology of untreated and gemcitabine-treated SW1990 gemcitabine-resistant cells and normal SW1990 cells were compared. NF-κB p65 expression was knocked down using siRNA. Vimentin and E-cadherin expression were analyzed using western blotting, and CD24+CD44+, CD133+ cells were quantified by FACS. Additionally, immunohistochemistry of EMT-associated markers and stem cell-associated markers were performed in 41 cases of human pancreatic ductal adenocarcinoma. In SW1990 gemcitabine-resistant cells, gemcitabine induced a mesenchymal cell phenotype, expression of EMT-related molecular markers and increased CD24+CD44+ and CD133+ cells compared to untreated SW1990 gemcitabine-resistant and SW1990 cells. Knockdown of NF-κB p65 inhibited the ability of gemcitabine to increase the proportion of CD24+CD44+ or CD133+ cells and expression of EMT-related molecular markers. In human pancreatic ductal adenocarcinoma, significant correlations were observed between expression of the EMT-associated markers vimentin and E-cadherin, and stem cell-associated markers CD24, CD133 and CD44. This study demonstrated that EMT correlated with CD24+CD44+ and CD133+ cells in pancreatic cancer. This study also suggests that EMT may induce cancer stem-like cells in pancreatic cancer, with different degrees of EMT probability inducing different proportions of CD24+CD44+ and CD133+ cells.     

The impact of CD4+CD25+ Treg on tumor specific CD8+ T cell cytotoxicity and cancer

There is sufficient evidence to suggest that tumor growth elicits specific immune responses, including CD8(+) and CD4(+) T cell responses that may delay tumor growth and could potentially be harnessed to eradicate cancer. Nevertheless the frequent outcome of cancer is lethality associated with uncontrolled growth and dissemination of tumor cells. The failure of the immune response may be naturally programmed and related to a specific subpopulation of CD4(+)CD25(+) regulatory T cells, whose function is to protect us against autoimmunity. Recent investigations have shed light on the in vivo behavior and functions of these cells. It is becoming evident that a major impact of these cells is on the cytolytic action of specific CD8(+) T cells that target the tumor. Inhibition of cytotoxicity is dependent on TGF-beta signaling by the effector cells. Thus, targeting immune regulation may provide a promising approach to the immune therapy of cancer. This approach however could also have unexpected deleterious consequences, as surprising new observations indicate that regulatory T cells can also delay tumor growth by independent mechanisms that relate to their cross talk with the innate immune response to cancer.     

CD4 + CD25 + 调节性T细胞与肿瘤免疫治疗

 CD4＋CD25＋调节性T淋巴细胞（regulatory Tcell，Treg）是一类具有独特免疫调节功能的T淋巴细胞亚群，一般占人外周血CD4＋T细胞的5％～15％。近年来，国内外对这类调节性T细胞的研究已从自身免疫耐受、移植免疫逐渐扩展到肿瘤免疫，认为Treg是形成肿瘤免疫耐受的关键成分。     

CD+4CD+25调节性T细胞与肿瘤免疫

 近期研究发现一个有独特免疫调节功能的T细胞亚群：CD+4 CD+25调节性T细胞,不仅能抑制自身免疫性疾病发生,还参与肿瘤免疫的调节。这群细胞具有免疫无能和免疫抑制特性,与肿瘤免疫逃逸有密切的关系。肿瘤环境中CD+4 CD+25调节性T细胞增加,导致肿瘤免疫失调,去除这群细胞可有效诱导肿瘤免疫,为肿瘤治疗提供了一种新的思路。     

CD4^＋CD25^＋调节性T细胞与肿瘤的相关性研究

通过了解CD4^＋CD25^＋调节性T细胞（CD4^＋CD25^＋Treg）表面分子的特性和CD4^＋CD25^＋Treg在外周血和组织中的表达,认识CD4^＋CD25^＋Treg在肿瘤免疫调节中的作用,探索其作用的分子机制。     

Ex vivo expansion of CD8+CD56+ and CD8+CD56- natural killer T cells specific for MUC1 mucin

Prostate cancers express MUC1, but nearly all metastatic cells lack HLA class I molecules. Thus, a lymphocyte population that can sense its antigenic environment, while also able to react to stimuli of natural killer (NK) cells, may be a more versatile effector cell population for antitumor immune responses. Herein, we report that tumor-specific MUC1 peptide, interleukin 2, and interleukin 12 act synergistically to stimulate the ex vivo expansion of CD8(+)CD56(-) T cells and CD8(+)CD56(+) natural killer T (NKT) cells from the peripheral blood mononuclear cells of prostate cancer patients, as well as healthy male and female donors. Both the CD56(+) NKT cells and CD56(-) T cells lysed allogeneic mucin-bearing target cells, as well as NK target cells, but not lymphokine-activated killer target cells. However, the CD56(+) NKT cells displayed a 2-fold greater cytolytic activity than the CD56(-) T cells. The mucin-specific cytolytic activity and NK cytolytic activities for both lymphocyte populations were independent of HLA class I and CD1 molecules. The CD56(-) T cells up-regulated CD56 with continued antigenic stimulation in the presence of interleukin 12, suggesting that CD8(+)CD56(-) T cells are NKT cells. However, CD56(+) NKT cells expand poorly to continued stimulation. All mucin-stimulated NKT cells exhibited the activated/memory CD45RO phenotype. The NKT cell lines express the alpha/beta T-cell receptor (TCR). The TCR repertoire was limited and varied with cell line, but was not the V alpha 24V beta 11 TCR typically associated with NKT cells. Whereas CD161 is generally considered a marker of NKT cells, the mucin-stimulated NKT cells did not express this marker. Thus, we have described two phenotypically distinct NKT types that do not display a biased TCR repertoire, but do display specificity for a tumor-specific peptide antigen (CTL-like activity), as well as HLA class I-deficient target cells (NK-like activity).