树突状细胞疫苗联合胸腺肽α1对人源化免疫重建裸鼠结肠癌生长的抑制效应

目的观察胸腺肽αl（Ted）联合结肠癌细胞裂解物致敏树突状细胞（LyDCs）对人源化免疫重建裸鼠结肠癌的免疫治疗效应。方法常规DCs负载结肠癌细胞裂解物制备LyDCs疫苗，流式细胞仪（FCM）检测Tαl体外刺激前、后的LyDCs表型。HT-29结肠癌裸鼠模型成瘤后，经尾静脉注射人外周血T淋巴细胞6×10^6个／只，2d后，FCM检测裸鼠外周血人源性CD4^＋、CD8^＋T细胞；将人源化免疫重建裸鼠分为3组，分别用LyDCs＋Tctl、LyDCs和生理盐水皮下免疫注射治疗；治疗后7d，体外观察各组裸鼠脾脏淋巴细胞的肿瘤杀伤作用及IFN-γ、IL4分泌水平，实验结束时，观察LyDCs联合Tctl对荷瘤裸鼠的体内抑瘤作用。结果LyDCs的表型HLA．DR、CD80、CD86、CD83较刺激前明显上调；免疫重建裸鼠均检测到人源性CD4^＋、CD8^＋T细胞；LyDCs＋Tctl组裸鼠脾脏T淋巴细胞的肿瘤杀伤作用与LyDCs组比较差异有统计学意义（P〈0．01），LyDCs＋Ted组T细胞的IFN-γ分泌水平与LyDCs组比较差异有统计学意义（P〈0．01）；接种HT-29细胞58d后，LyDCs＋Tαl组、LyDCs组抑瘤率分别为60．41％、37．20％，两组之间抑瘤效应比较差异有统计学意义（P〈0．01），两组的抑瘤效应与对照组比较分别（P〈0．01）。结论Tαl能增强LyDCs诱导的CD4^＋，Th1细胞反应和CTLs杀伤效应，对DCs疫苗的抗癌免疫治疗功效具有明显的放大作用。     

白细胞介素-18与癌细胞裂解物修饰的树突状细胞疫苗对胰腺癌的免疫治疗作用

目的　观察经白细胞介素 18(IL 18)和胰腺癌细胞裂解物修饰的树突状细胞 (DC)疫苗对胰腺癌荷瘤小鼠的免疫治疗作用。方法　用药物诱导制成BALB/c小鼠的胰腺癌模型。通过IL 18和癌细胞裂解物修饰小鼠DC(MTSC4) ,制成DC疫苗 ,检测各组血清中细胞因子IL 18、干扰素γ(IFN γ)的浓度 (分为DC IL18 裂解物组 ,DC 裂解物组 ,DC IL 18组 ,DC组 ,PBS组 ) ,研究了其对小鼠胰腺癌的免疫治疗作用。结果　DC IL18 裂解物组中IL 18与IFN γ的浓度 ( 2 161± 43 9)μg/L和 ( 4 3 5± 72 ) μg/L ,与其余各组比较差异有显著性 (P <0 .0 5 ,P <0 .0 1)。DC IL18 裂解物组接种胰腺癌细胞后 5 0d均未见移植肿瘤形成 ,与其余各组比较差异有非常显著性 (P <0 .0 1)。对胰腺癌细胞的细胞毒作用以DC IL18 裂解物组最强 ,DC 裂解物组次之 ,DC IL18组较弱 ,其余 2组则缺乏 (P <0 .0 1)。DC IL18 裂解物组的小鼠的生存期比他各组明显延长 ,且肿瘤的重量比其他各组明显减轻 (P <0 .0 1,P <0 .0 5 )。结论　IL 18和胰腺癌细胞裂解物修饰的DC疫苗对胰腺癌荷瘤小鼠有明显的免疫治疗作用。     

树突状细胞在肿瘤免疫治疗中的作用

现代肿瘤疫苗战略是建立在由肿瘤特异抗原细胞毒T细胞(CTL)介导的免疫应答在抗肿瘤过程中起主导作用的这一原则[1]基础上的。肿瘤免疫应答并不是由肿瘤直接传递抗原给T细胞,而是要先把肿瘤抗原递呈至一种特殊的细胞——专职抗原递呈细胞(APC),如树突状细胞(DC),递呈抗原给T细胞,使其能识别肿瘤细胞,从而消灭肿瘤。     

肿瘤提取物冲击致敏树突状细胞治疗脑胶质瘤的研究

目的　研究肿瘤细胞提取物体外冲击致敏的树突状细胞 (DC)回输对颅内荷瘤小鼠的免疫治疗效应。方法　将 72只昆明种小鼠随机分 4组 ,分别进行磷酸盐缓冲液 (PBS)、未经致敏的DC、G42 2肿瘤细胞提取物、DC疫苗皮下接种 ,每组各取 6只小鼠脾细胞进行细胞毒性T淋巴细胞 (CTL)体外诱导及活性检测。其余 48只颅内接种G42 2胶质母细胞瘤。另取 48只昆明种小鼠颅内荷瘤后 ,随机分 4组 ,分别进行PBS、未经致敏的DC、G42 2肿瘤细胞提取物、DC疫苗皮下接种。观察各组小鼠的生存时间 ,小鼠死亡后行病理学检查。结果　疫苗能诱导产生针对G42 2肿瘤抗原特异性CTL ,差异具有非常显著性 (P <0 .0 1)。接种疫苗后荷瘤 ,PBS、未经致敏的DC、G42 2肿瘤细胞提取物组、DC疫苗组生存期分别为 ( 2 1.42± 1.86)d、( 2 4.0 0± 2 .3 6)d、( 2 2 .75±1.89)d、( 3 2 .42± 3 .80 )d ,疫苗组小鼠能明显抵抗G42 2的再次攻击 (P <0 .0 1) ;DC疫苗回输免疫接种至荷瘤小鼠 ,PBS、未经致敏的DC、G42 2肿瘤细胞提取物组、DC疫苗生存期分别为 ( 17.0 0±1.62 )d、( 17.5 8± 1.80 )d、( 16.92± 2 .2 0 )d、( 2 2 .0± 3 .12 )d ,疫苗组生存期明显较对照组延长(P <0 .0 5 )。结论　DC疫苗免疫接种至颅内荷瘤小鼠能显著地诱导机体产生抗原     

树突状细胞与肿瘤的免疫治疗

肿瘤免疫治疗作为恶性肿瘤综合治疗的重要手段日益受到人们的重视和关注，在几种免疫治疗中，利用以细胞为基础的疫苗进行的主动免疫疗法，近年来正逐渐成为免疫学家和肿瘤学家的研究热点，细胞疫苗的高免疫原性可以诱导宿主产生特异性的抗肿瘤免疫，阻止肿瘤的形成、生长、扩散和复发，甚至消除肿瘤。     

树突状细胞与膀胱癌的治疗进展

树突状细胞（DC）是人体内抗原递呈能力最强的细胞，由DC激活的T细胞介导的免疫应答在机体抗肿瘤过程中起着主导作用，本文订对DC的生物学特性，DC参与抗肿瘤的机制，膀胱癌病人DC的变化及目前DC对膀胱癌免疫治疗的研究进展作一综述。     

肿瘤细胞RNA加载树突状细胞治疗前列腺癌的实验研究

目的 将小鼠前列腺癌细胞株(RM-1)的RNA加载树突状细胞(dendritic cell,DC),探讨其体内外诱导特异性CTL反应和抗肿瘤免疫的作用.方法 将RM-1细胞的RNA作为肿瘤抗原加载小鼠骨髓来源的DC,构建DC瘤苗(RNA-DC);混合淋巴细胞反应(MLR)检测DC瘤苗刺激T细胞的增殖能力,MTT法检测DC瘤苗诱导特异性CTL的杀伤活性;ELISA法测定DC瘤苗诱导细胞因子IL-2和IFN-γ的作用;体内实验检测DC瘤苗的抗前列腺癌免疫治疗作用和免疫保护作用.结果 DC瘤苗刺激T细胞增殖能力明显增强,能够诱导小鼠产生特异性CTL,对RM-1肿瘤细胞具有明显杀伤作用,细胞上清液中IL-2和IFN-γ的水平升高;经RNA-DC治疗的荷瘤小鼠瘤体生长减慢,存活期延长.DC瘤苗对小鼠具有免疫保护作用,能有效抵抗肿瘤细胞的攻击.结论 将前列腺癌细胞RNA加载DC,能够有效诱导抗肿瘤免疫反应和免疫保护功能,为前列腺癌的DC免疫治疗提供了良好的实验基础.     

基于树突状细胞的前列腺癌的免疫治疗

近年来，肿瘤的免疫治疗日益受到人们的重视。其中树突状细胞(DC)更是成为研究热点。迄今为止，免疫治疗已应用于黑色素瘤和肾癌等肿瘤的治疗中。有关DC疫苗治疗前列腺癌的动物实验及临床应用已有大量文献报道。本文就有关方面的新进展进行综述。     

树突状细胞与肝癌免疫治疗进展

树突状细胞 (dendritic cells,DC)是指具有树枝状形态 ,膜表面高表达 MHC 和 类分子以及多种辅助分子 (如CD5 4、CD80、CD86等 ) ,能有效摄取、加工和处理抗原并激活初始型 T细胞的一类细胞。作为目前发现的功能最强的专职抗原提呈细胞 (antigen presenting cells,APC) ,DC是抗原特异性免疫应答的始动者 ,在调控机体的免疫应答以及抗肿瘤过程中发挥重要作用。肝细胞癌 (HCC)是高度恶性肿瘤之一 ,目前尚缺乏有效的治疗。以 DC为基础的肝癌免疫治疗日益受到重视 ,取得了初步成果。本文就 DC在肿瘤免疫中的作用机制及其应用于 HCC…     

树突状细胞疫苗与肝癌免疫治疗进展

以肿瘤疫苗为基础的主动免疫治疗和以T细胞介导的抗肿瘤免疫应答成为肿瘤治疗新的热点,近来发现,肝癌患者癌灶缺乏成熟而有活性的CD8+树突状细胞(dendriticcells,DC),表明肝癌发生过程中有活性DC的浸润作用[1]。DC是机体免疫系统中功能最强的专职性抗原提成细胞(Antigen-presentingcells,APC),其最大特点是能激活初始型T细胞(CD4+Th细胞和CD8+CTL细胞),生成辅助性T细胞和杀伤性T细胞,DC能识别、加工、提呈抗原,表达高水平MHC类分子,共刺激分子,粘附分子,同时分泌高水平的IL-12,从而主导初始型T细胞生成Th1型应答,Th1型应答在…     

Immunoregulation of Dendritic Cell Subsets by Inhibitory Receptors in Urothelial Cancer

Blockade of inhibitory receptors (IRs) overexpressed by T cells can activate antitumor immune responses, resulting in the most promising therapeutic approaches, particularly in bladder cancer, currently able to extend patient survival. Thanks to their ability to cross-present antigens to T cells, dendritic cells (DCs) are an immune cell population that plays a central role in the generation of effective antitumor T-cell responses. While IR function and expression have been investigated in T cells, very few data are available for DCs. Therefore, we analyzed whether DCs express IRs that can decrease their functions. To this end, we investigated several IRs (PD-1, CTLA-4, BTLA, TIM-3, and CD160) in circulating CD1c⁺ DCs, CD141⁺ DCs, and plasmacytoid DCs from healthy donors and patients with urothelial cancer (UCa). Different DC subsets expressed BTLA and TIM-3 but not other IRs. More importantly, BTLA and TIM-3 were significantly upregulated in DCs from blood of UCa patients. Locally, bladder tumor–infiltrating DCs also overexpressed BTLA and TIM-3 compared to DCs from paired nontumoral tissue. Finally, in vitro functional experiments showed that ligand-mediated engagement of BTLA and TIM-3 receptors significantly reduced the secretion of effector cytokines by DC subpopulations. Our findings demonstrate that UCa induces local and systemic overexpression of BTLA and TIM-3 by DCs that may result in their functional inhibition, highlighting these receptors as potential targets for UCa treatment.

Immunity in Cancer

Evidence from studies of experimental and human tumours confirms that the major component of the tumour rejection response is the circulating small long-lived lymphocyte. In vivo antibody response to tumour antigen may result in enhancement of cancer growth rate, and possibly competes with cell-mediated surveillance and rejection in the genesis of tumours. The host defect in cellular immunity which allows tumours to become established and grow is probably a general body phenomenon rather than one peripherally located in the draining lymph-nodes. In the case of breast cancer this dysfunction is closely related to other endocrine factors. Immunotherapy remains an adjunct to other forms of treatment of solid tumours. The basis of immunotherapy requires maximum repression of cellular immune rejection, with simultaneous minimal production of potentially enhancing antibody.     

Histiocytic and Dendritic Cell Neoplasms

This article reviews the features of dendritic cells (DCs) of myeloid-derived, plasmacytoid, and follicle-associated types and tumors of these cells, as well as myeloid sarcoma. The morphologic and immunophenotypic features in this group of neoplasms is featured, including mature neoplasms such as Langerhans cell histiocytosis, its malignant counterpart Langerhans cell sarcoma, and S100-negative histiocytic proliferations. More immature or precursor malignancies in this group include myeloid and monocytic leukemias presenting in extramedullary tissues as well as the newly codified blastic plasmacytoid dendritic cell neoplasm. Although likely not related histogenetically to myeloid-derived DCs, mesenchymal-type lymph node tumors including follicular dendritic cell and fibroblastic reticulum sarcomas are also discussed. All of these neoplasms can exhibit a range of immunophenotypic and morphologic features that underscore the plasticity of the non-neoplastic precursors from which they are derived.     

前列腺癌组织中树突状细胞的变化及以此为基础的免疫治疗

树突状细胞(DC)作为功能最为强大的抗原呈递细胞,对肿瘤免疫起着关键的启动作用。前列腺癌细胞通过一系列复杂的作用使肿瘤免疫微环境中DC的数目和功能发生变化,从而逃逸机体的免疫监视,形成了肿瘤的发生、发展。认识到这一点,人们开展以DC为基础的前列腺癌的免疫疫苗治疗,并取得了一定的效果。而前列腺癌免疫微环境中DC的变化和以此为基础的免疫治疗仍处于起步阶段。