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(交流）树突状细胞技术交流平台

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树突状细胞技术交流平台
导言:树突状细胞是目前所知的功能最强大的专职抗原提呈细胞。由于其具有激活初始T细胞的能力，因而被认为是机体免疫的始动者，在抗肿瘤免疫方面起着重要的作用。近年来,随着免疫学技术的发展,树突状细胞的相关研究日益火暴。本人长期从事DC的研究，但在实际工作中依旧会遇到许多不好解决困难，相信许多同人也会有类似的麻烦。因此，我希望借丁香园建立这个树突状细胞技术交流平台，以便于大家的讨论及交流。

树突状细胞的体外诱导扩增技术

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2005-01-15 13:34 浏览 : 7927 回复 : 11

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野原编辑于 2005-01-15 20:59

• 文献求助

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树突状细胞的相关文献：
树突状细胞与自身免疫性甲状腺疾病
吴佩文< 综述
国外医学内分泌学分册2001 年7月第21卷第4 期

2005-05-10 20:17

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• 普放病例分享31：X线虽有不足但有用，请各位上眼（1楼43楼已更新图像）

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树突状细胞

2005-05-10 20:21

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• 【心电旋律 13】25岁的心脏真的“红旗飘飘”了？（公布答案：嗜铬细胞瘤）

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树突状细胞与肿瘤免疫治疗相关文献：
1. 标题：树突状细胞激活的肿瘤浸润性淋巴细胞体外对自体肝癌细胞杀伤活性的研究
著者：刘剑勇; 张力图; 李挺等
著者单位：南宁广西医科大学附属肿瘤医院 530021
中文摘要：目的:探讨树突状细胞(DC)激活的肿瘤浸润性淋巴细胞(TIL)体外对自体肝癌细胞杀伤活性。方法:从肝癌患者外周血获取DC,应用粒/巨噬细胞集落刺激因子(GM-CSF)、白细胞介素-4(IL-4)和肿瘤抗原激活DC,然后用DC来激活TIL,观察TIL在体外对自体肝癌细胞的杀伤活性。结果:DC激活的TIL具有很高的对自体肝癌细胞杀伤活性,杀伤率为(89.39±3.05)%,明显高于未经DC激活的TIL、CD激活的T淋巴细胞和未经DC激活的T淋巴细胞对自体肝癌细胞的杀伤率。结论:肝癌患者外周血DC能诱导TIL产生高效而特异的抗肝癌免疫。
出处：广西医科大学学报 2002.04.15; 19(2): 154-156

2. 标题：转基因树突状细胞激活细胞毒性T细胞特异性杀伤淋巴瘤的体外实验
著者：张耀; 张伟京; 朱平
著者单位：军事医学科学院附属307医院肿瘤二科 100039
中文摘要：目的:探讨转基因树突状细胞激活细胞毒性T细胞产生抗淋巴瘤的特异性细胞免疫反应。方法:采用人骨髓来源的髓系前体细胞,在人细胞因子IL-4、GM-CSF和TNF-α诱导下,在体外生成大量树突状细胞。将制备好的含有IgVH1核酸质粒,用脂质体法转染树突状细胞。转染成功的树突状细胞与外周血T淋巴细胞共培养,激活特异性CTL细胞,与阳性表达IgVH1的人淋巴瘤Namalwa细胞反应,用3H-TdR掺入法观察CTLS对瘤细胞的特异性杀伤效应。结果:树突状细胞能够用脂质体方法转染IgVH1核酸质粒,并且有效递呈给外周血T细胞,对表达IgVH1的人淋巴瘤Namalwa细胞产生特异性免疫杀伤活性,与对照组相比差异有显著意义(P<0.01)。结论:体外诱导扩增的DC能够转染IgVH1核酸质粒,体外激活T淋巴细胞,产生特异性细胞毒效应。
出处：中国生物制品学杂志 2002.07.20; 15(4): 193-196

3. 标题：白血病细胞系来源的树突状细胞诱导及其抗肿瘤免疫功能研究
著者：罗云萍; 李用国; 蔡大川等
著者单位：重庆医科大学检验系 400016
中文摘要：树突状细胞(DC)在抗肿瘤免疫反应中起关键作用,但大多数白血病病人有DC功能缺陷。在体外扩增DC并增强其抗肿瘤免疫功能及以DC为基础的肿瘤疫苗是对白血病有效的免疫治疗方法。为了探讨由不同的髓性白血病细胞系诱生DC的条件及其抗白血病反应,选用HL-60, K562和THP-1细胞与不同的细胞因子组合诱生DC,以光学和电子显微镜术观察形态特征,用流式细胞术和单克隆抗体检测细胞表型,以同种混合淋巴细胞反应观察刺激淋巴细胞增殖,用51Cr释放法检测诱生细胞的细胞毒作用,用ELISA法测定DC培养及DC+血单个核细胞联合培养的血清中IL-12及IFN-γ的量。结果表明,由K562,HL-60和THP-1细胞诱生的DC具有树突状细胞的形态学特征,细胞表达DC的表面分化抗原,其中GM-CSF+IL-4+TNF-γ刺激HL-60-DC和THP-1-DC和GM-CSF+IL-4+IL-12刺激的K562-DC中有抗原表达。3种细胞诱生的DC对混合淋巴细胞反应及CTL反应有强刺激作用。诱生DC的培养上清和DC与血单个核细胞共培养上清中分别测出不同量的IL-12和IFN-γ。结论提示,细胞因子能诱导髓性白血病细胞产生DC,不同细胞需要不同的细胞因子和培养条件。这些DC表达抗原呈递细胞的表型具有刺激T淋巴细胞增殖和诱导CTL反应以及分泌IL-12和促进T细胞分泌IFN-γ的作用。
出处：中国实验血液学杂志 2002.06.25; 10(3): 229-235

4. 标题：肝癌组织内树突状细胞及淋巴细胞浸润的临床意义
著者：殷晓煜; 吕明德; 梁力建等
著者单位：广州中山大学附属第一医院肝胆外科 510080
中文摘要：目的:探讨肝细胞性肝癌(HCC)组织内树突状细胞及淋巴细胞浸润的临床意义。方法:收集1995年1月-1996年7月在本院接受肿瘤根治性切除术的44例HCC患者的临床病理资料,采用免疫组织化学方法检测HCC组织内树突状细胞浸润的数目,同时评估淋巴细胞的浸润情况,分析两者与肝癌切除术后肿瘤复发时间及生存率之间的关系。结果:发现肿瘤组织内树突状细胞数≥20、同时伴淋巴细胞浸润(+)者(A组,n=17)术后肿瘤复发时间显著晚于不同时具备上述两项条件者(B组,n=27),两者复发的中位期分别为21.6个月和4.1个月(U值=105.5,P=0.009)。A组术后1、3、4年生存率分别为83.5%、61.8%和48.7%,B组分别为42.2%、28.4%和23.0%,A组均显著高于B组(Logrank=7.68,P=0.006)。结论:HCC组织内树突状细胞及淋巴细胞浸润情况与临床预后密切相关,是直接影响预后的独立因素。
出处：中华外科杂志 2002.05.22; 40(5): 336-338

5. 标题：胃腺癌局部淋巴结树突状细胞对转移和预后的影响
著者：姜汉国; 唐慰萍; 曹军等
著者单位：湛江广东医学院病理教研室 524023
中文摘要：目的:研究胃腺癌局部淋巴结中树突状细胞(DC)对转移和预后的影响。方法:将S-100蛋白作为DC特异性标记物,应用S-P免疫组化方法检测胃腺癌局部淋巴结中DC的数量和分布。结果:转移组淋巴结中DC较非转移组明显增多。在57例转移组中,DC显著者18例,5例生存率55.56%;DC不明显者39例,5年生存率23.08%。30例非转移组中,DC显著者19例,5年生存率73.68%;DC不明显者11例,5年生存率36.36%。经χ2检验,在上述两组中,DC显著者的转移和5年生存率较DC不明显者差异均有显著性意义(P<0.05)。结论:胃腺癌局部淋巴结中DC程度同转移和预后密切相关。
出处：宁夏医学杂志 2002.07.15; 24(7): 390-391

6. 标题：乳腺癌细胞抗原和自身淋巴结树突状细胞对细胞因子诱导的杀伤细胞作用研究
著者：巩新建; 刘军权; 陈复兴等
著者单位：徐州中国人民解放军97医院普外科 221004
中文摘要：目的:从乳腺癌患者淋巴结中分离和定向诱导培养扩增树突状细胞(DC),观察其经自身肿瘤细胞抗原冲击后对自身细胞因子诱导的杀伤细胞(CIK)杀伤活性的影响。方法:取手术切除肿瘤周围转移的淋巴结,提取单个核细胞,将贴壁生长的细胞用细胞因子基因重组粒巨集落生长因子(rhGM-CSF)、基因重组白介素4(rhIL-4)、基因重组α-肿瘤坏死因子(rhTNF-α)联合诱导培养DC,然后用自身肿瘤细胞抗原冲击DC并作用CIK,最后检测CIK杀伤3种靶细胞(自身乳腺癌细胞、K562和SGC-7901细胞)的活性。结果:乳腺癌患者转移淋巴结中的贴壁细胞,经细胞因子联合诱导培养,DC含量可达15.3%-37.0%。经自身肿瘤抗原冲击的淋巴结DC活化的CIK,杀伤自身肿瘤细胞活性达71.3%,单纯CIK为37.0%,两者比较差异有显著性(P<0.01);而对K562和SGC-7901细胞杀伤活性无明显差异。结论:肿瘤周围转移淋巴结贴壁细胞在体外能定向诱导扩增出大量DC;DC经自身肿瘤抗原冲击后能明显提高CIK对自身肿瘤细胞的杀伤活性。
出处：南京医科大学学报 2002.03.05; 22(2): 144-146

7. 标题：树突状细胞在喉癌及癌前病变中的表达及意义
著者：陶雁玲; 崔永华
著者单位：武汉华中科技大学同济医学院附属同济医院耳鼻喉科 430030
中文摘要：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(CD45RA、CD45RO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CD45RA抗原低表达而CD45RO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。
出处：肿瘤防治研究 2002.06.05; 29(3): 210-211

8. 标题：树突状细胞浸润与肺癌预后相关性研究
著者：赵瑞景; 冯惠东; 王秀荣等
著者单位：石家庄河北医科大学微生物与免疫学教研室 050017
中文摘要：目的:研究肿瘤浸润树突状细胞(TIDC)在肺癌组织中的数量,以及与肺癌生物学行为的关系和对预后的价值。方法:用免疫组化法检测39例肺癌组织S-100蛋白表达水平,流式细胞仪检测S-100+TIDC的数量及DNA倍体。结果:39例标本中S-100蛋白阳性表达率为100%,S-100+细胞具有典型树突状细胞形态学特征。异倍体肿瘤组织中S-100+TIDC百分率为21.81%±8.18%,明显高于二倍体肿瘤组织(16.03%±4.75%)。有淋巴结转移组S-100+TIDC百分率为20.43%±7.74%,无淋巴结转移组为19.41%±7.76%;肿瘤大于或等于3cm组S-100+TIDC百分率为20.90%±8.65%,小于3cm组为19.70%±7.61%;非小细胞肺癌组S-100+TIDC百分率为19.48%±7.98%,小细胞肺癌组为21.74%±6.17%;存活期小于1年组S-100+TIDC百分率为21.96%±8.05%,1-3年组为19.47%±6.18%,大于3年组为19.14%±8.76%。经统计学分析,S-100+TIDC数量与肿瘤大小、组织学类型、淋巴结转移情况及患者生存期之间均未见明显相关性。结论:TIDC数量在人类肺癌中不宜作为一个独立的预后指标。
出处：中国肺癌杂志 2002.04.20; 5(2): 112-114

9. 标题：胃癌组织中树突状细胞浸润及其表面分子表达的临床意义
著者：王正昕; 张明徽; 李楠等
著者单位：第二军医大学长征医院普通外科 200003
中文摘要：目的:研究胃癌组织中树突状细胞(dendritic cells,DC)浸润及其表面分子表达的临床意义。方法:采用酶消化胃癌组织,分离细胞后进行免疫组化S-100染色和流式细胞术分析,研究15例胃癌组织中DC的浸润及其表面分子表达与胃癌病理分期的关系,并通过RT-PCR技术分析了IL-10、VEGF和TGF-β1等免疫抑制因子在胃癌细胞中的表达。结果:胃癌组织中DC的数量少,而且其表面分子如MHCⅡ类分子、共刺激分子B7-1和粘附分子ICAM-1等呈低表达或不表达,DC的数量及其表面分子的表达与胃癌的病理分期负相关。免疫抑制因子IL-10、VEGF和TGF-β1在胃癌细胞中有高水平的表达。结论:提示胃癌组织中DC的浸润及表面分子表达与胃癌病理分期关系密切。
出处：第二军医大学学报 2002.03.30; 23(3): 264-266

10. 标题：肿瘤抗原致敏树突状细胞瘤苗治疗颅内胶质瘤的实验研究
著者：刘福生; 王忠诚; 历俊华等
著者单位：北京市神经外科研究所 100050
中文摘要：目的:研究肿瘤抗原致敏树突状细胞瘤苗治疗胶质瘤的疗效。方法:从大鼠的骨髓中加入GM-CSF和IL-4培养树突状细胞,采用相差显微镜、扫描电镜观察了树突状细胞的形态学特点;免疫组织化学双标技术、流式细胞免疫学技术观察了其特异性抗体OX6和OX62的表达;微酸洗脱方法抽提C6肿瘤抗原体外致敏树突状细胞,建立C6胶质瘤脑内动物模型,体内应用抗原致敏的树突状细胞,观察脑内肿瘤的疗效,并取致敏的动物的脾脏T细胞体外加入C6肿瘤抗原,加入IL-2培养进行CTL活性检测。结果:培养第8天可见有典型的树突状细胞;免疫组织化学双标可见有OX6和OX62阳性细胞,流式细胞免疫学分析发现OX62阳性率为93.03%,OX6的阳性率为92.01%;体外细胞毒试验发现对相应的C6肿瘤细胞有明显的杀伤作用;动物实验发现实验组可见肿瘤组织内有大量的坏死,而对照组仅有少量的坏死,两者相比P<0.01。结论:体内注射采用微酸洗脱的抗原肽致敏树突状细胞瘤苗能够引起荷瘤动物脑肿瘤大面积的坏死,该方法为将来临床免疫治疗胶质瘤充分调动机体的免疫系统奠定基础。
出处：中华神经外科杂志 2002.03.30; 18(2): 91-95

11. 标题：树突状细胞肿瘤疫苗诱导抗胃癌作用的实验研究
著者：雷晓; 余佩武; 石彦等
著者单位：第三军医大学附属西南医院普通外科 400038
中文摘要：目的:探讨树突状细胞(dendritic cells,DCs)肿瘤疫苗诱导的抗胃癌效应对荷瘤裸小鼠的作用。方法:使用胃癌细胞冻融抗原,体外致敏从小鼠骨髓诱导分化来源的DCs成为肿瘤疫苗,用其来刺激脾脏淋巴细胞,得到肿瘤抗原特异的细胞毒性T淋巴细胞(CTL),观察其对荷瘤裸小鼠肿瘤生长的影响以及早期凋亡诱导作用。结果:经重组小鼠粒细胞巨噬细胞集落刺激因子(rmGM-CSF)和重组小鼠白细胞介素4(rmIL-4)体外诱导小鼠骨髓细胞,得到大量形态典型、具备强烈刺激增殖能力、高表达CD1a、CD11c、CD40和CD80的DCs。肿瘤抗原致敏DCs刺激脾脏淋巴细胞成为CTL后,可显著抑制裸小鼠皮下移植瘤生长并致瘤细胞早期凋亡增加。结论:DCs肿瘤疫苗可通过CTL的作用,抑制荷瘤裸小鼠的胃癌细胞生长及促进胃癌细胞早期凋亡。
出处：中华胃肠外科杂志 2002.03.25; 5(1): 45-48

12. 标题：小鼠肝癌总RNA转染的树突状细胞体外诱导特异性细胞毒T淋巴细胞的研究
著者：王国强; 钟翠平; 傅继东等
著者单位：复旦大学医学院组织学与胚胎学教研室 200032
中文摘要：目的:探讨小鼠骨髓树突状细胞(dendritic cell,DC)体外经Hepa 1-6肝癌细胞株总RNA转染后,对特异性细胞毒T淋巴细胞(CTL)的诱导作用。方法:自小鼠骨髓分离DC前体细胞,经GM-CSF+IL-4培养、扩增;制备Hepa 1-6小鼠肝癌细胞株总RNA,体外转染DC,检测DC诱导同基因型小鼠T细胞增殖及其特异性CTL的反应能力。结果:经Hepa 1-6肝癌细胞总RNA转染的DC,其组织相容性分子(MHC-Ⅰ、Ⅱ)及共刺激分子(B7-1、B7-2)表达明显增高,刺激同基因型小鼠T细胞增殖能力增强,且能诱导Hepa 1-6特异性CTL。结论:以肝癌总RNA转染DC,构造肝癌疫苗为肝癌的临床治疗提供了新的策略。
出处：中国免疫学杂志 2002.02.20; 18(2): 102-105

13. 标题：前列腺癌肿瘤微环境树突状细胞与T细胞免疫的关系
著者：丘少鹏; 陈辉熔; 邓春华等
著者单位：广州中山医科大学附属第一医院泌尿外科 510080
中文摘要：目的:了解前列腺癌组织树突状细胞与肿瘤微环境T细胞免疫的关系。方法:对22例前列腺癌组织和周围正常前列腺组织用S100、CD3、CD21和CD14mAb分别作SP免疫组化染色,光镜下对阳性细胞计数并计算细胞指数,对癌组织S100+和CD3+细胞指数行相关性分析。结果:前列腺癌组织和正常组织可观察到S100+DCs和CD3+T细胞分布,而CD21+B细胞和CD14+单核/巨噬细胞均少见。癌组织中S100+DCs指数和CD3+T细胞指数均明显少于周围正常组织(P<0.05),癌组织S100+DCs指数与CD3+T细胞指数呈正相关(r=0.86,P<0.05)。结论:DCs是前列腺癌肿瘤微环境中的主要抗原提呈细胞,癌组织DCs数量减少可能与前列腺癌肿瘤微环境T细胞免疫功能低下有关。
出处：中山医科大学学报 2002.03.15; 23(2): 127-128

14. 标题：肿瘤DC疫苗临床应用研究现状
著者：郭建巍，蔡美英
出处：中国肿瘤 2002（2）：97-100

15. 标题：树突状细胞技术在肿瘤临床治疗中的应用
著者：李焱，洗励坚
出处：癌症 2002（4）：443-6

16. TI: Tumour cell-dendritic cell fusion for cancer immunotherapy: comparison
of therapeutic efficiency of polyethylen-glycol versus electro-fusion protocols.
AU: Lindner,-Matthias; Schirrmacher,-V
AD: University Hospital for Gynecology and Obstetrics, Voss-Strasse 9, 69115 Heidelberg, Germany. matthias_lindner@med.uni-heidelberg.de
SO: Eur-J-Clin-Invest. 2002 Mar; 32(3): 207-17
AB: BACKGROUND: Fusion of tumour cells with dendritic cells (DC) is a powerful new technology to increase tumour vaccine immunogenicity. The aim of this study was to compare fusion protocols with syngenic DCs with respect to the efficiency of polyethylen-glycol-(PEG) and electric pulse-mediated fusions for induction of protective anti-tumour immune responses. As a model we chose a low immunogenic and metastatic murine mammary carcinoma cell line, which mimics clinically relevant tumour features. METHODS: FACS-staining, chromium release assay, therapeutic immunization, adoptive transfer. RESULTS: We show that the parental line with low cell surface expression of MHC molecules as well as a lacZ transfectant becomes highly immunogenic upon fusion with DCs. This was true for PEG- as well as for electro-fused cells. Immunization with products of DCs and tumour cells cocultivated for 16 h without the fusing agent PEG also caused induction of profound anti-tumour immunity, while this was not the case when using parental tumour cells or their lacZ transfectants as vaccines. Immune protection against the parental tumour cells after vaccination with fused cells was long-lasting and could be transferred via immune spleen cells into immuno-incompetent nude (nu/nu) mice. CONCLUSION: Fusion products of DA3(hi) mammary carcinoma cells and DCs produced by an electric pulse were similar to those produced by PEG fusion with regard to vaccine potency in prophylactic antitumour immunization assays in vivo. Therefore, both techniques seem to be promising for clinical application.

17. TI: A dendritic cell vaccine induces protective immunity to intracranial growth of glioma.
AU: Insug,-O; Ku,-Geoffrey; Ertl,-Hildegund-C-J; Blaszczyk-Thurin,-Magdalena
AD: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
SO: Anticancer-Res. 2002 Mar-Apr; 22(2A): 613-21
AB: The central nervous system is an immunologically privileged site hidden behind the blood brain barrier. Nevertheless, immune effector cells induced peripherally can be recruited into the central nervous system. Active immunotherapy of intracranial malignancies is thus potentially feasible. In this study we describe a vaccine regimen, based on bone marrow-derived dendritic cells pulsed with the RNA derived from GL261 glioma cells that induces a specific T cell response and protection against intracerebrally implanted GL261 tumors. Immunohistochemical analysis of brain tumors from vaccinated mice was characterized by pronounced intratumoral infiltrates predominantly of CD4+ as well as CD8+ T cells. The efficacy of the vaccine was improved further by administration of recombinant interleukin-12 into the vaccine regimen.

18. TI: Dendritic cells in human squamous cell carcinoma of the oral cavity.
AU: Kikuchi,-Kentaro; Kusama,-Kaoru; Taguchi,-Kohei; Ishikawa,-Fumitaka; Okamoto,-Motoyoshi; Shimada,-Jun; Saka***a,-Hideaki; Yamamo,-Yoshiro
AD: 1st Department of Oral and Maxillofacial Surgery, Meikai University School of Dentistry, Sakado, Saitama, Japan. kenta@cb3.so-net.ne.jp
SO: Anticancer-Res. 2002 Mar-Apr; 22(2A): 545-57
AB: Dendritic cells (DCs) are antigen-presenting cells that initiate and modulate immune responses, including tumor immunity. In this study we examined, immunohistochemically, the distribution of DC subsets in the primary tumor, adjacent tissue and regional lymph nodes (RLNs) of patients with oral squamous cell carcinoma (OSCC). The numbers of S100+ and CD1a+ DCs in tissue adjacent to the primary tumor were greater in patients without metastasis to RLNs (PN- cases), compared with those with metastasis (PN+ cases), while greater numbers of CD83+ DCs in the primary tumors were found in PN+ cases. In the RLNs, the numbers of S100+ and CD1a+ DCs were less in PN+ cases than in PN- cases, while the numbers of CD83+ DCs were greater in PN+ cases compared with those in PN- cases. These results suggest that the distribution of DC subsets in OSCC may reflect the degree of tumor immunity induced in the host bearing OSCC.

19. TI: Vaccination with autologous tumour antigen-pulsed dendritic cells in advanced gynaecological malignancies: clinical and immunological evaluation of a phase I trial.
AU: Hernando,-Juan-Jose; Park,-Tjoung-Won; Kubler,-Kirsten; Offergeld,-Ruth; Schlebusch,-Harald; Bauknecht,-Thomas
AD: Department of Obstetrics and Gynaecology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. j.hernando@uni-bonn.de
SO: Cancer-Immunol-Immunother. 2002 Mar; 51(1): 45-52
AB: Dendritic cell (DC)-based therapy has proven to be effective in patients with malignant lymphoma, melanoma, and renal and prostate carcinoma. In this phase I clinical trial, we have shown that patients with advanced gynaecological malignancies can be effectively vaccinated with DC pulsed with keyhole limpet haemocyanin (KLH) and autologous tumour antigens. Two patients with uterine sarcoma and six subjects with ovarian carcinoma received three to 23 intracutaneous injections of antigen-pulsed DC at 10-day or 4-week intervals. Three patients showed stable disease lasting 25 to 45 weeks, and five experienced tumour progression within the first 14 weeks. KLH- and tumour lysate-specific delayed-type hypersensitivity (DTH) reactions were observed in six and one patient, respectively. Lymphoproliferative responses to KLH and to tumour lysate stimulation were recorded in six patients and in two patients respectively. Tumour antigen-stimulated interferon-gamma (IFN-gamma) secretion by peripheral blood mononuclear cells (PBMC) in one patient was consistent with a T(H) type 1 cytokine bias. The treatment was safe, well tolerated, immunologically active and except for local cutaneous hypersensitivity devoid of significant adverse effects.

20. TI: Paucity of dendritic cells in pancreatic cancer.
AU: Dallal,-Ramsey-M; Christakos,-Peter; Lee,-Kenneth; Egawa,-Shinichi; Son,-Young-Ik; Lotze,-Michael-T
AD: Department of Surgery and Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
SO: Surgery. 2002 Feb; 131(2): 135-8
AB: BACKGROUND: The number of dendritic cells (DC) in the local tumor environment correlates with patient survival in numerous tumors. The relationship of DC infiltration in the tumor microenvironment and prognosis was examined in patients with pancreatic adenocarcinoma. METHODS: Forty-seven pancreatectomy specimens with a diagnosis of pancreatic adenocarcinoma were identified retrospectively and analyzed with the dendritic cell markers S-100 and CD1a. Patient survival was correlated with these markers and with p53, CD3, CD20, CD68, Ki-67. RESULTS: Significant numbers (>3 per high-powered field) of tumor-associated S100(+) or CD1a(+) cells were found in only 2/47 patients (4%). When present, dendritic cells were located outside the margin of the tumor. CD3, CD68, and CD20 positive cells were rare or absent in 96%, 92%, and 93% of the specimens. A correlation with survival and numbers of immune cells could not be made secondary to their rarity. The median survival was 18.9 months. No other indices measured correlated with survival. CONCLUSIONS: In patients with pancreatic adenocarcinoma, there is a paucity of immune cells within the tumor.

21. TI: Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors.
AU: Heiser,-Axel; Coleman,-Doris; Dannull,-Jens; Yancey,-Donna; Maurice,-Margaret-A;Lallas,-Costas-D;Dahm,-Philipp; Niedzwiecki,-Donna; Gilboa,-Eli; Vieweg,-Johannes
AD: Cancer Immunotherapy Program, Division of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
SO: J-Clin-Invest. 2002 Feb; 109(3): 409-17
AB: Autologous dendritic cells (DCs) transfected with mRNA encoding prostate-specific antigen (PSA) are able to stimulate potent, T cell-mediated antitumor immune responses in vitro. A phase I trial was performed to evaluate this strategy for safety, feasibility, and efficacy to induce T cell responses against the self-protein PSA in patients with metastatic prostate cancer. In 13 study subjects, escalating doses of PSA mRNA-transfected DCs were administered with no evidence of dose-limiting toxicity or adverse effects, including autoimmunity. Induction of PSA-specific T cell responses was consistently detected in all patients, suggesting in vivo bioactivity of the vaccine. Vaccination was further associated with a significant decrease in the log slope PSA in six of seven subjects; three patients that could be analyzed exhibited a transient molecular clearance of circulating tumor cells. The demonstration of vaccine safety, successful in vivo induction of PSA-specific immunity, and impact on surrogate clinical endpoints provides a scientific rationale for further clinical investigation of RNA-transfected DCs in the treatment of human cancer.

2005-05-10 20:33

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