树突状细胞与肝细胞癌免疫治疗

树突状细胞（DC）是体内功能最强的抗原提呈细胞（APC）,由DC激活的T细胞免疫在抗肿瘤过程中起着主导作用。关于DC肿瘤疫苗的基础与临床研究结果显示,DC疫苗在恶性肿瘤治疗中具有良好的应用前景。     

树突状细胞与肝细胞癌免疫治疗

树突状细胞(DC)是体内功能最强的抗原提呈细胞(APC),由DC激活的T细胞免疫在抗肿瘤过程中起着主导作用。关于DC肿瘤疫苗的基础与临床研究结果显示,DC疫苗在恶性肿瘤治疗中具有良好的应用前景。     

肿瘤DC疫苗临床应用研究现状

树突状细胞（DC）是体内功能最强的抗原提呈细胞，由DC激活的T细胞免疫在抗肿瘤过程中起着主导作用。关于DC肿瘤疫苗临床应用的结果显示出DC疫苗在恶性肿瘤治疗中有巨大的应用前景。本文将国内外有关DC疫苗临床应用的最新进展作一综述。     

树突状细胞及其在血液系统肿瘤免疫治疗中的应用

树突状细胞(DC)是体内功能最强的抗原提呈细胞,由DC激活的T细胞免疫在抗肿瘤过程中起着主导作用。关于DC肿瘤疫苗在血液系统肿瘤免疫治疗方面应用的结果已显示出DC疫苗在血液系统肿瘤治疗中有巨大的应用前景。就国内外有关DC的生物学特征和DC疫苗在血液系统肿瘤免疫治疗中的研究进展作一综述。     

基因修饰的树突状细胞应用于肿瘤免疫治疗的研究进展

树突状细胞（dendritic cells,DC）被认为是目前人体内最重要的、抗原呈递能力最强的抗原呈递细胞（antigen-presentingcell,APC）,是体内唯一能活化静息T淋巴细胞的APC,是机体免疫应答的始动者,在抗肿瘤免疫中发挥着极其重要的作用。近些年来,基因修饰DC疫苗的出现,弥补了单纯DC功能的不足,增强了其抗肿瘤作用,本文将对基因修饰DC疫苗的抗肿瘤作用作一简要综述。     

树突状细胞的肿瘤抗原负载

树突状细胞（DC）是体内功能最强的专职抗原提呈细胞，在诱导特异性抗肿瘤免疫反应中起着至关重要的作用。通过体外负载肿瘤抗原致敏DC可以有效地增强其抗原提呈能力，所制备的肿瘤抗原DC疫苗回输体内后可促进机体产生特异性细胞毒T淋巴细胞（CTL）和其他抗肿瘤免疫应答机制，有效地杀伤肿瘤细胞。目前已发展了多种针对DC负载肿瘤抗原的方法，有些方法已被应用到了人体肿瘤治疗。     

树突状细胞免疫治疗的新进展

树突状细胞(DC)为目前发现的体内最强的专职抗原提呈细胞,但在体内并不能进行充分的交叉提呈.目前可通过在体外制备DC疫苗或者与化疗等促凋亡治疗联用的方法,增强DC的抗原提呈能力,提高机体免疫系统的抗肿瘤作用.     

树突状细胞肿瘤免疫研究进展

树突状细胞(DC)是目前已知机体内功能最强大的抗原提呈细胞,能诱导特异性的细胞毒性T淋巴细胞生成.大量研究表明,DC在机体免疫应答及抗肿瘤免疫巾发挥重要作用.目前,以DC为基础的肿瘤免疫治疗及DC疫苗等方面已取得较大进展,作为一种新的抗肿瘤治疗手段显现出良好的临床应用前景.     

树突状细胞疫苗的临床应用进展

树突状细胞(DC)是一类重要的抗原呈递细胞,其独特的刺激幼稚T细胞活化的功能,使其在抗严重病毒感染和抗肿瘤免疫方面发挥极其重要的作用.目前多种形式以DC为基础的肿瘤疫苗已在动物模型中取得了较好的抗肿瘤效果,部分疫苗已应用于临床试验.现就DC疫苗近几年的临床应用进展作一综述.     

CpG ODN加强树突状细胞疫苗抗Lewis肺癌的研究

目的　探讨CpGODN对树突状细胞 (DC)疫苗抗肿瘤作用的影响。方法　应用ODN182 6作为DC的成熟刺激信号 ,体外控制DC充分成熟 ,以混合或融合的方式将肿瘤抗原负载于DC制备DC疫苗。以特异性杀伤细胞活性和淋巴细胞增殖反应测定疫苗的体外免疫活性 ,并将疫苗经小鼠腹腔注射 ,观察治疗和预防实验肿瘤的生长情况。结果　经ODN 182 6刺激后的DC细胞形态呈成熟状态 ,流式细胞仪分析检测刺激前后DC细胞表面分子CD4 0的表达分别为 11和 2 4 (MFI) ,CD86的表达分别为 33和 75 (MFI) ,刺激后的DC培养上清中IL 12的分泌水平为刺激前的 10倍。刺激后DC融合疫苗组CTL活性、T淋巴细胞增殖活性及体内Lewis肺癌移植瘤的抑瘤率均明显高于未刺激的DC融合组 (P <0 .0 5 )。结论　CpGODN能通过诱导DC成熟 ,增强DC疫苗的抗肿瘤作用 ,有效诱导机体产生特异的抗肿瘤反应。未成熟的DC可通过与肿瘤细胞混合的方式 ,获得较好的抗原捕获效果 ,产生一定的抗肿瘤效应 ,而对于刺激成熟的DC则需通过融合手段负载抗原 ,达到有效的抗肿瘤活性。     

树突状细胞临床治疗实体瘤：峰回路转

肿瘤免疫细胞疗法展现了良好的临床抗肿瘤前景。树突状细胞（DC）识别肿瘤抗原作为机体免疫响应的关键起始步骤,捕获肿瘤抗原后分化成熟,在淋巴结将抗原信号提呈给CD4+ T细胞、CD8+ T细胞等免疫细胞,激发抗肿瘤效应,应用于肿瘤治疗,尤其是实体瘤,被寄予厚望。但由于实体瘤TME复杂的结构特点、DC和T/B 细胞免疫响应的机制不清晰等问题犹如崇山峻岭摆在眼前,故未能形成关键理论和技术突破。以CAR-T 细胞为代表的精准细胞免疫疗法已表现出优势,但仍面临抗原选择瓶颈。DC治疗性疫苗在临床试验中表现出良好的疗效和安全性,随着DC在TME中关键作用机制的进一步揭示,研究者的目光重新聚焦在DC抗肿瘤效应,推动着DC与其他手段的联合疗法、工程化DC疫苗等实体瘤治疗方案从基础向临床转化,目前正迈入DC临床治疗实体瘤的新阶段。本文系统地对DC治疗实体瘤的临床研究进展、实体瘤TME中DC的种类及其抗肿瘤机制、工程化DC疫苗,以及面临的挑战和应对策略等问题进行了评述。     

In vitro immunization of patient T cells with autologous bone marrow antigen presenting cells pulsed with tumor lysates

Presentation of cell-associated antigen to T cells is a critical event in the initiation of an anti-tumor immune response but it appears to often be deficient or limiting. Here we report an experimental system for stimulation of human T lymphocytes using autologous antigen presenting cells (APCs) and autologous tumor cells. Two types of APCs were prepared from human bone marrow: MC and DC. MC were produced by using GM-CSF and SCF. DC were obtained with the same cytokines plus IL-4. DC and MC were generated in parallel from the same patients and their phenotypes and capacities to prime T lymphocytes were analyzed and compared. MC were CD14+, CD1a-, CD33+ and HLA-DR+. Two populations of DC were defined: immature DC were uniformly CD1a-; mature DC expressed CD1a, CD80, CD86, HLA-DR, CD54 and CD58 but lacked surface CD14. Stimulation of autologous T lymphocytes was studied by measuring their proliferation and cytotoxic function. In more than 80% of our experiments the proliferation of autologous T lymphocytes cocultured with APC pulsed or not with tumor cell lysates was higher than that of T cells cultured alone. DC were more effective than MC in stimulating proliferation of lymphocytes. The capacity of a patient's autologous bone marrow-derived APC to stimulate T cells when exposed to autologous tumor cell lysates suggest that such antigen-exposed APC may be useful in specific anti-tumor immunotherapy protocols.     

NK cell-based immunotherapy: new prospects and involvement of dendritic cells

Dendritic cells (DC) were initially described as antigen presenting cells able to prime naive T cells. In fact, dendritic cells are also able to activate natural killer (NK) cells. The crosstalk between DC and NK is now regarded as a main stage in the initiation of innate and adaptative immune responses. Moreover, DC mediated-NK cell activation is particularly efficient since DC promote both effector functions and survival or proliferation of NK cells. Furthermore, recent publications in the field of NK cell biology underscore a role for NK cells in anti-tumor effects. NK cell-based immunotherapy should be reconsidered Here, we will report how pioneering immunotherapy trials based on natural cytotoxicity and progress in NK cell biology can promote NK cells in anti-tumor immune responses. Then, we will discuss the biological features of the DC/NK crosstalk and its implementations in immunotherapy protocols.     

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。     

Dendritic cell vaccination with a toll-like receptor agonist derived from mycobacteria enhances anti-tumor immunity

Dendritic cell (DC)-based vaccines are considered useful in cancer immunotherapy, and the interaction of DC and adjuvants is important in the design of the next generation vaccines. In this study, whether DC combined with Rv2299c derived from mycobacteria could improve anti-tumor immune responses in a colon cancer mouse model was evaluated. MC38 cell lines were injected subcutaneously to establish colon-cancer-bearing mice and the following four groups were evaluated: PBS control, tumor antigen (TA) loaded-DC, Rv2299c, and a combination of TA-loaded-DC and Rv2299c. The combination treatment with TA-loaded-DC and Rv2299c exhibited greater inhibition of tumor growth compared to other groups. These effects were associated with the reduction of suppressor cells, such as myeloid-derived suppressor cells and regulatory T cells, and the induction of effector cells, such as CD4⁺ T cells and CD8⁺ T cells, in spleen, and with the activation of cytotoxic T Lymphocytes and NK cells. These results suggest that TA-loaded-DC vaccination with Rv2299c derived from mycobacteria enhanced anti-tumor immunity in a mouse colon cancer model by inhibiting the generation of immune-suppressive cells and recovering numbers of effector cells, and demonstrated superior polarization of the Th1/Th2 balance in favor of the Th1 immune response.     

不同亚型树突状细胞之间的作用在肿瘤免疫中的研究进展

树突状细胞（dendritic cells，DCs）作为专职抗原呈递细胞，被认为是连接天然免疫与获得免疫的桥梁，在诱发获得性免疫和免疫耐受调节中发挥着重要作用。经典Ⅰ型DCs（conventional DC1， cDC1）被认为在抗肿瘤免疫应答以及交叉呈递中发挥尤为关键的作用。然而，DCs各亚群的功能特异性以及亚群之间的相互作用在进一步强化抗肿瘤免疫应答中的作用不可忽视。本文就DCs亚群之间的作用在肿瘤免疫中的研究进展进行综述，以期为以DCs为靶点的肿瘤免疫治疗提供新的思路。      

Influence of drug-induced apoptotic death on processing and presentation of tumor antigens by dendritic cells

Here we have studied the effects of apoptotic cell death induced by chemotherapic agents on tumor phagocytosis by dendritic cells (DC) and presentation of the relevant antigen to T lymphocytes. Annexin-V-FITC (Ann-V) and propidium iodide (PI) staining was used to assess early apoptotic (Ann-V(+)/PI(-)) vs. late apoptotic/secondary necrotic (Ann-V(+)/PI(+)) death after a 24 hr observation of untreated and drug-treated gastric carcinoma cells. After treatments, the HLA-A*0201(+) tumor cell line KATO III was exposed for 24 hr to allogeneic, HLA-related GM-CSF, IL-4-driven immature (i) DC. Tumor-loaded iDC were tested for IL-12 release in an ELISA assay, incubated with the DC-maturating factor TNF-alpha and used as stimulators for autologous T lymphocytes. Generation of antitumor T response against KATO cells was evaluated in an anti-MHC class I MAb-blocked Interferon-gamma ELISPOT assay. After treatment with Cis-platin (cis), all dying cells were in early apoptosis, whereas secondary necrosis was the prevalent death pattern observed after epirubicin (epi) and doxorubicin (doxo). Doxo and epi increased tumor expression of heat shock protein (hsp) 70 and uptake of tumor cell components by DC, whereas cis treatment had no effect on hsp70 and was associated with poor tumor uptake by DC. Significant upmodulation of IL-12 was observed by DC that had taken up the doxo- and epi-treated tumors (p< 0.005 and p< 0.01, respectively). Increased IFN-gamma release was also observed after stimulation of T lymphocytes with DC loaded with doxo- and epi-treated (p< 0.02 and p< 0.005, respectively) but not with cis-treated DC. These data show that the products of early apoptosis cannot efficiently cross-activate MHC class I-restricted anti-tumor lymphocytes even in the presence of DC maturating factors, whereas secondary necrosis is associated with robust T cell response.     

Dendritic cell vaccination for cancer therapy.

A growing list of defined tumor-antigens opens the way to antigen specific immunotherapy of cancer. However current approaches are often limited in their potential to induce an effective anti-tumor response. Dendritic cells (DC) are natural adjuvants for the induction of antigen specific T cell response. They have been successfully used in clinical pilot trials to induce tumor specific immunity as well as clinical response in selected patients. Current research focuses on optimization of DC source, choice of antigen, antigen loading, mode of injection, as well as immuno-monitoring. Finally, a variety of immune escape mechanisms are operative at the tumor site and have to be overcome for successful vaccination.     

体外诱导的粘蛋白抗原特异性细胞毒性T淋巴细胞抗乳腺癌的研究

目的 制备携带粘蛋白(MUC1)抗原基因的重组腺相关病毒(AAV/MUC1),研究其感染树突状细胞(DC)所诱导的细胞毒性T淋巴细胞(CTL)特异性杀伤肿瘤细胞的活性.方法 应用分子生物学方法制备高低度的重组腺相关病毒(AAV/MUC1).AAV/MUC1体外感染外周血单核细胞,诱导分化为DC.DC与T淋巴细胞混合,刺激产生CTL.流式细胞技术检测DC和CTL的分化和功能指标,MTS方法检测CTL的杀伤活性和特异性.结果 成功制备的重组病毒(AAV/MUC1)滴度为6×1010拷贝/ml.感染单核细胞率为84.27%.所获得的CTL对MUC1阳性的乳腺癌细胞株的杀伤率为(46.32±0.07)%.其杀伤作用具有MUC1抗原特异性和MHC-I类分子限制性的特征.结论 以MUC1抗原为靶点的CTL可有效地杀伤乳腺癌细胞,为乳腺癌提供了一条新的治疗途径.     

以树突状细胞疫苗为基础的肿瘤免疫治疗

树突状细胞（DC）是目前发现的人体内功能最强的专职抗原呈递细（APC），近年来，以DC为基础的肿瘤免疫治疗越来越引起人们的重视，本文就Dc生物学特征、Dc瘤疫苗分类、抗瘤机制、抗原负载或转染方法、优缺点及其临床研究作一综述。