树突状细胞在食管癌T细胞抗肿瘤免疫中的作用

目的：了解食管癌组织中树突状细胞（ＤＣｓ）在肿瘤浸润性Ｔ淋巴细胞激活中的作用。方法：采用免疫组化和ＲＴ－ＰＣＲ的方法,对４６例食管癌手术标本中ＤＣｓ（ＣＤ１ａ）、Ｔ细胞亚群（ＣＤ３、ＣＤ４、ＣＤ８、ＣＤ２５）及共刺激因子Ｂ７进行检测。结果：癌组织中的ＤＣｓ与ＣＤ３＾＋、ＣＤ４＾＋Ｔ细胞有相关性,与ＣＤ８＾＋、ＣＤ２５＾＋Ｔ细胞无明显关系,且Ｂ７ｍＲＮＡ表达均为阴性。结论：食管癌中ＤＣｓ不一定能有效     

膀胱肿瘤抗原致敏的树突状细胞诱导 T 淋巴细胞抗肿瘤效应的研究

目的：研究经膀胱肿瘤抗原致敏后的树突状细胞（Dc）对T淋巴细胞的激活、增殖作用及对T24膀胱肿瘤细胞的抑癌效应。方法：分离健康供血者外周血单个核细胞及T淋巴细胞，联合应用粒／巨噬细胞集落刺激因子（GM—CSF）及白介素-4（IL-4）从单个核细胞中培养出Dc，以人膀胱癌细胞系T24肿瘤细胞裂解物刺激Dc，检测经膀胱肿瘤抗原致敏后的DC对T淋巴细胞的细胞增殖动力学影响并用M1rr显色法测定致敏Dc诱导的T淋巴细胞对T24膀胱肿瘤细胞体外的抗肿瘤效应。结果：膀胱癌细胞裂解物致敏的Dc可诱导T淋巴细胞强烈的增殖反应，与对照组比较具有显著性差异（P〈0．01）；增殖后的T淋巴细胞对T24膀胱肿瘤细胞有明显的细胞毒作用。结论：经膀胱肿瘤抗原致敏的Dc能诱导产生显著的T淋巴细胞增殖，在体外有明显的抑癌效应。     

膀胱肿瘤抗原致敏的树突状细胞诱导T淋巴细胞抗肿瘤效应的研究

目的：研究经膀胱肿瘤抗原致敏后的树突状细胞（Dc）对T淋巴细胞的激活、增殖作用及对T24膀胱肿瘤细胞的抑癌效应。方法：分离健康供血者外周血单个核细胞及T淋巴细胞，联合应用粒／巨噬细胞集落刺激因子（GM—CSF）及白介素-4（IL-4）从单个核细胞中培养出Dc，以人膀胱癌细胞系T24肿瘤细胞裂解物刺激Dc，检测经膀胱肿瘤抗原致敏后的DC对T淋巴细胞的细胞增殖动力学影响并用M1rr显色法测定致敏Dc诱导的T淋巴细胞对T24膀胱肿瘤细胞体外的抗肿瘤效应。结果：膀胱癌细胞裂解物致敏的Dc可诱导T淋巴细胞强烈的增殖反应，与对照组比较具有显著性差异（P〈0．01）；增殖后的T淋巴细胞对T24膀胱肿瘤细胞有明显的细胞毒作用。结论：经膀胱肿瘤抗原致敏的Dc能诱导产生显著的T淋巴细胞增殖，在体外有明显的抑癌效应。     

树突状细胞与抗肿瘤免疫

树突状细胞（ＤＣ）是一种重要的专职抗原提呈细胞（ＡＰＣ）,在抗肿瘤免疫中发挥重要作用。目前有关ＤＣ在白血病和其它肿瘤治疗中作用的研究已成为该领域的研究热点,有望在肿瘤免疫治疗中取得新的突破。     

肝癌细胞抗原致敏树突状细胞诱导的体外抗肿瘤作用

目的　探讨原发性肝癌患者外周血树突状细胞 (DC)经自体肝癌细胞抗原致敏后诱导的体外抗肿瘤作用。方法　对肝癌患者外周血采用密度梯度离心法分离 ,获得DC前体细胞 ,用重组人粒细胞 巨噬细胞集落刺激因子 (rhGM CSF)和重组人白细胞介素 4(rhIL 4)联合培养 ,诱导扩增DC。制备自体肝癌细胞抗原 ,体外脉冲DC ,检测DC诱导自体T细胞增殖能力及细胞毒性T细胞 (CTL )在体外对自体肝癌细胞的杀伤活性 ,并检测肿瘤抗原致敏DC分泌的IL 12水平。结果　经自体肝癌细胞抗原致敏的DC能分泌IL 12和诱导较强的自体T细胞增殖 ,且能诱导特异性CTL ,该CTL对自体肝癌细胞具有很强的杀伤活性 ,杀伤率显著高于DC、未经肝癌细胞抗原致敏的DC激活的CTL及T淋巴细胞的杀伤率 ,而对CT 2 6细胞、BEL 740 2细胞无明显的杀伤作用。结论　肝癌患者外周血DC经自体肝癌细胞抗原致敏后能诱导高效而特异的抗肝癌免疫 ,其机制可能与增强T细胞应答和诱导机体产生肿瘤特异CTL从而发挥特异性的抗肿瘤作用有关。     

中药影响树突状细胞抗肿瘤免疫作用的研究进展

1树突状细胞及其功能树突状细胞(dendritic cell,DC)因其形态而得名,是目前已知的功能最强大的抗原提呈细胞(antigen-presenting cell,APC),它们可以加工处理抗原并以抗原肽-MHCⅡ类分子复合物的形式将抗原信息提呈给T细胞,特别是能激活初始型T细胞,诱发特异性免疫应答。其激活T细胞的能力是巨噬细胞的100~10000倍。DC起源于多能造血干细胞,分为髓样DC和淋巴样DC两种(也有人称之为DC1、DC2),两者表达的抗原及功能不同,DC1主要诱导Th0向Th1分化,而DC2主要诱导Th0向Th2分化。DC广泛分布于脑以外的全身各组织,但是数量很少,不足外…     

树突状细胞的体外扩增和抗肿瘤免疫

树突状细胞（DC）是体内最重要的抗原提呈细胞,具有独特的免疫学功能,综述了DC分离,体外扩增,鉴定和功能检测方法的研究现状,分析了DC与肿瘤免疫的关系,以及DC抗肿瘤治疗的应用前景。     

树突状细胞体外诱导抗肿瘤免疫

目的以树突状细胞（DC）在体外诱导抗肝癌免疫。方法自肝癌患者外周血中分离DC;以粒／巨噬细胞集落刺激因子（GM－CSF）及白介素-4（IL－4）联合刺激DC;以人肝癌细胞系HepG2细胞的肿瘤相关抗原（TAA）激活DC;DC诱导自体T淋巴细胞增殖、分化为细胞毒性T细胞（CTL）;检测CTL及其上清液对HepG2细胞、BEL－7402细胞、LOVO细胞及HOS－8603细胞的细胞毒作用。结果经人肝癌细胞系HePG2细胞的TAA激活并经GM－CSF及IL－4联合刺激后,肝癌患者外周血DC能够诱导自体T淋巴细胞增殖分化为CTL,该CTL及其上清液对HePG2细胞均有高效杀伤作用（杀伤率分别为92％±10％和41％±8％）,对BEL－7402细胞亦有较强的杀伤力（杀伤率分别为56％±10％和31％±9％）,对SGC－7901细胞、LOVO细胞及HOS－8603细胞则无明显的细胞毒作用。结论肝癌患者外周血DC体外能够诱导高效而特异抗肝癌免疫。提示DC可能在肿瘤治疗及预防其复发和转移中发挥重要作用。     

Efficient antitumor immunity derived from maturation of dendritic cells that had phagocytosed apoptotic/necrotic tumor cells

Dendritic cells (DCs) that acquired antigen from apoptotic tumor cells are able to induce major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes and antitumor immunity. In the present study, we investigated the efficiency of antitumor immunity derived from DCs that had phagocytosed apoptotic/necrotic BL6-10 melanoma cells compared with that of DCs pulsed with the tumor mTRP2 peptide. Our data showed that phagocytosis of apoptotic/necrotic tumor cells resulted in maturation of DCs with up-regulated expression of proinflammatory cytokines [interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha, interferon-gamma and granulocyte-macrophage colony-stimulating factor], chemokines (MIP-1alpha, MIP-1beta and MIP-2), the CC chemokine receptor CCR7 and the cell surface molecules (MHC class II, CD11b, CD40 and CD86), and down-regulated expression of the CC chemokine receptors CCR2 and CCR5. These mature DCs displayed enhanced migration toward the CC chemokine MIP-3beta in a chemotaxis assay in vitro and to the regional lymph nodes in an animal model in vivo. Our data also showed that vaccination with DCs that had phagocytosed apoptotic/necrotic BL6-10 cells was able to (i) more strongly stimulate allogeneic T-cell proliferation in vitro, (ii) induce an in vivo Th1-type immune response leading to more efficient tumor-specific cytotoxic CD8(+) T-cell-mediated immunity and (iii) eradicate lung metastases in all 6 vaccinated mice compared with mice vaccinated with DCs pulsed with the tumor mTRP2 peptide, in which lung metastases were reduced (mean number of 16 per mouse) but not completely eradicated. Therefore, DCs that had phagocytosed apoptotic/necrotic tumor cells appear to offer new strategies in DC cancer vaccines.     

基于树突状细胞的肿瘤免疫治疗研究进展

树突状细胞(dendritic cells,DC)是目前已知最强的抗原递呈细胞.近年来,人们对DC在肿瘤免疫治疗中的作用等研究取得了快速发展,大量研究资料表明DC在肿瘤特异性免疫反应过程中起重要作用.本文主要对DC的生物学特性、抗肿瘤机制及临床应用作一介绍.     

基于树突状细胞的肿瘤免疫治疗研究进展

树突状细胞（dendritic cells,DC）是目前已知最强的抗原递呈细胞。近年来,人们对DC在肿瘤免疫治疗中的作用等研究取得了快速发展,大量研究资料表明DC在肿瘤特异性免疫反应过程中起重要作用。本文主要对DC的生物学特性、抗肿瘤机制及临床应用作一介绍。     

Direct injection of immature dendritic cells into irradiated tumor induces efficient antitumor immunity

Although there are several ways to load tumor antigens to DCs, in vitro preparation of tumor antigens and manipulation of DCs are usually required. Therefore, to develop a simple antitumor immunization method, we examined if direct injection of DCs into tumor apoptosed by ionizing IR could induce efficient antitumor immunity. Ionizing IR with 15 Gy induced apoptosis in tumor maximally after 6 hr. Injection of DCs i.t. into IR tumor induced strong cytotoxicity of splenocytes against tumor cells compared to i.t. injection of DCs or ionizing IR of tumor, both of which induced weak cytotoxicity. In an animal study, i.t. injection of DCs into IR tumor induced therapeutic antitumor immunity against a tumor established at a distant site. Moreover, when TNF-alpha or LPS was added as a danger/maturation signal to DC suspension before i.t. injection, antitumor immunity was significantly potentiated compared to a group treated with i.t. injection of DCs into IR tumor. Our results suggest that injection of DCs into tumor apoptosed by ionizing IR might be a simple and efficient method of immunization against tumor.     

树突状细胞在喉癌及癌前病变中的表达及意义

 目的　树突状细胞 (DCs)在喉癌及癌前病变中的表达及意义。方法　用免疫组化法检测 39例喉癌及癌前病变标本中DCs分布特点、DCs表面HLA DR的表达 ,以及肿瘤浸润性T淋巴细胞 (CD4 5RA、CD4 5RO表达 )免疫状态。结果　喉重度上皮不典型增生与喉鳞状细胞癌的DCs数量明显增多、呈簇状分布。前者T淋巴细胞CD4 5RA抗原低表达而CD4 5RO抗原高表达 ;喉癌组织中结果恰相反。结论　喉重度上皮不典型增生与喉鳞状细胞癌的DCs均增加 ,但喉癌DCs表面HLA -DR表达水平下降 ,与DCs免疫功能低下相关 ,一定程度上影响T细胞的激活     

Vaccination of fusion cells of rat dendritic and carcinoma cells prevents tumor growth in vivo

Several reports on immunotherapy using dendritic cells-based vaccine have been published. We investigated findings using fusion cells (FCs) generated from rat dendritic cells and a syngeneic hepatic cancer cell line with regard to inducing anti-tumor immunity. Vaccination of rats using FCs protected against growth of the subcutaneously implanted tumor in vivo and induced infiltration of CD8(+) T cells into the tumor. At the site of CD8(+) T cell infiltration, there were apoptotic tumor cells. T cells from spleen of FCs-vaccinated rats with protective ability against tumor growth included tumor specific cytotoxic CD8(+) T cells restricted to major histocompatibility complex Class I. In addition, adaptive transfer of in vitro re-stimulated splenic T cells with FCs was effective in preventing tumor growth and in vivo vaccinations of rats with FCs after resection of the subcutaneous implanted tumor inhibited local tumor recurrences. Immunotherapy using FCs appears to be an effective method if used in combination with surgical or other anti-cancer therapies.     

IL-18基因增强肿瘤抗原致敏DC诱导的CTL特异性杀伤肝癌细胞

目的:探讨腺病毒介导的白细胞介素18(IL18）基因转染能否使肿瘤抗原冲击的树突状细胞(dentritic cell,DC) 在体外诱导出更强的抗肝癌免疫反应。方法：携IL18 的重组腺病毒载体感染经肝癌细胞株HepG2冻融抗原致敏的DC(AdIL18HepG2/DC), FACS分析AdIL18HepG2/DC表面分子的表达, ELISA法检测IL18的分泌水平, 3HTdR掺入法检测T淋巴细胞增殖能力, MTT法检测细胞毒性T 淋巴细胞杀伤效应。结果： AdIL18HepG2/DC较未转染DC能高水平地表达CD1a、CD11c、CD80、CD86以及HLADR;较未经IL18转染的DC分泌较高水平的IL18。AdIL18HepG2/DC 能非常有效地刺激自体T 细胞增殖(CPM 值为228 018±1 079),其刺激强度显著强于AdIL18DC、HepG2/DC、AdlzcZ/DC及DC（均P＜0.05）。当靶细胞为HepG2时,AdIL18HepG2/DC诱导的CTL杀伤活性显著高于其他各组（均P＜0.05）,并且其杀伤能力与效应细胞数量成正比。结论： IL18 基因转染且肝癌抗原致敏的DC可以显著增强DC的特异性抗肝癌效应。     

封闭B7-H1分子对肿瘤浸润树突状细胞介导T细胞免疫功能的影响

目的:研究肿瘤浸润树突状细胞（tumorinfiltrating dendritic cell,TIDC）及脾脏树突状细胞（splenic dendritic cell,SDC）表面B7H1、B71、B72分子的表达情况;探讨封闭TIDC及SDC表面B7H1分子对其介导T细胞免疫功能的影响。方法： CD11c磁珠阳性分选法提取荷瘤小鼠的TIDC及SDC,流式细胞术检测其表面B7H1、B71、B72分子的表达情况。TIDC及SDC作为刺激细胞,脾脏T细胞作为反应细胞行混合淋巴细胞反应,同时加入B7H1抗体或其对照抗体,XTT比色法检测T细胞增殖指数,ELISA法检测T细胞分泌IL10的量。〖HT5W〗结果：〖HT5"SS〗B71及B72分子在TIDC表面的表达水平显著低于SDC（P<001）;B7H1分子在TIDC及SDC表面皆中度表达,表达水平无明显差异（P>0.05）。TIDC刺激T细胞增殖能力显著低于SDC,且诱导T细胞分泌更多的IL10。封闭DC表面B7H1分子后,TIDC刺激T细胞增殖能力显著提高（P<0.01）,且诱导T细胞分泌IL10的量明显减少（P<0.01）;SDC刺激T细胞增殖能力及诱导T细胞分泌IL10的量无明显变化（P>0.05）。结论：封闭DC表面的B7H1分子能显著提高TIDC活化T细胞的能力,可能解除TIDC介导的肿瘤免疫抑制     

食管癌组织中肿瘤浸润性树突状细胞表型改变及功能分析

目的:探讨食管癌患者肿瘤组织中肿瘤浸润性树突状细胞表型改变及功能。方法:收集2017年01月至2018年09月我院收治的食管癌患者92例作为观察组,选择同时期我院收治的92例食管良性肿物患者作为对照组。术中分别取食管癌标本和良性肿物标本。检测相应组织中肿瘤浸润性树突状细胞表达水平及表型,同时检测T细胞亚群表达情况,分析肿瘤浸润性树突状细胞表达情况和食管癌患者临床特征的相关性。结果:与对照组比较,观察组肿瘤浸润性树突状细胞密度、MHC-Ⅱ阳性树突状细胞和CD54阳性树突状细胞百分比均显著降低(P＜0.05);观察组CD4+T细胞增高［(24.81±3.72）% vs （20.77±3.63）%,P=0.000］;CD8+T细胞降低［(20.90±4.12）% vs （23.08±4.42）%,P=0.001］。食管癌组织中肿瘤浸润性树突状细胞密度、MHC-Ⅱ阳性树突状细胞和CD54阳性树突状细胞百分比与肿瘤直径、TNM分期和淋巴结转移有关(P＜0.05)。食管癌组织中肿瘤浸润性树突状细胞密度、MHC-Ⅱ阳性树突状细胞和CD54阳性树突状细胞与CD4+T细胞显著负相关,与CD8+T细胞显著正相关(P＜0.05)。结论:肿瘤浸润性树突状细胞在食管癌组织中低表达,功能低下,与T细胞亚群失衡和预后不良有关。     

Expression and significance of tumor infiltrating dendritic cells in renal cell carcinoma

Dendritic cells(DCs) are considered to be the most effective antigen-presenting cells(APCs) that play a major role in initiating the antitumor immune response. Tumor infiltrating dendritic cells(TIDCs) are DCs that exist in microenviroment of tumors. Although the function and significance of TIDCs in the immune response to tumor have never been clearly demonstrated, their location suggests that they play a critical role in the presentation of tumor antigen to specific T cells[1]. For the…