DCCIK细胞抗肿瘤的基础研究及临床应用进展

树突状细胞（dendritic cells，DC）分布于除脑和睾丸以外的身体的任何组织，是目前所知的功能最强大的专职抗原递呈细胞（antigen presenting cells，APC），亦是体内唯一具有激活幼稚T淋巴细胞诱导初次免疫应答能力的APC。     

树突状细胞胰腺癌免疫治疗新进展

胰腺癌早期诊断困难.临床常规治疗方法效果均欠佳[1].通过调节肿瘤抗原的递呈以增强抗肿瘤免疫应答是目前肿瘤免疫治疗的蕈要策略之一.树突状细胞(DC)作为功能强大的抗原递呈细胞和免疫反应启动者,与机体免疫状态密切相关,在胰腺癌免疫治疗中已显示出其独特的应用价值.     

树突状细胞疫苗治疗肝细胞癌的现状

树突状细胞（Dendritic cell，DC）是目前发现的抗原递呈功能最强的专职抗原递呈细胞，在抗肿瘤免疫中发挥着重要的作用。随着体外扩增DC和制备DC疫苗技术的发展，DC疫苗日益成为肝癌和其它肿瘤治疗的研究热点。本文就DC的生物学特性、肝癌患者DC的特点、抗原的负载方法及其研究现状等作一综述     

树突状细胞疫苗治疗慢性乙型肝炎的临床观察

形成慢性乙型肝炎的重要原因之一是树突状细胞（DC）功能缺陷。已知DC是功能最强的抗原递呈细胞，也是惟一能激活初始型T淋巴细胞的抗原递呈细胞，在T淋巴细胞介导的细胞免疫中起重要作用。当用特异性病毒抗原负载DC时，有可能通过诱导抗原特异细胞毒性T淋巴细胞（CTL）活性而特异性杀伤表达病毒抗原的靶细胞。     

抗原负载的树突状细胞激发肝癌免疫反应的临床研究

树突状细胞(dendritic cell,DC)是功能强大的抗原递呈细胞(APC).体外制备负载肿瘤抗原的DC瘤苗并注射回体内以激发机体抗肿瘤免疫是具有良好前景的生物治疗方案[1]. 一、材料与方法     

人外周血树突状细胞体外培养与扩增的研究进展

树突状细胞是机体内功能最强的抗原递呈细胞，目前其已成为肿瘤生物治疗的热点。如何激活树突状细胞和得到大量树突状细胞是以树突状细胞为基础的肿瘤主动免疫治疗的关键所在。近来树突状细胞的体外培养扩增技术日益成熟，但仍存在树突状细胞大量扩增方法的最优化和树突状细胞的异质性问题。本文介绍了树突状细胞的生物学特性、体外培养方法，体外扩增及其影响因素。     

不同树突状细胞亚型在支气管哮喘中的作用

树突状细胞(DCs)是目前已知功能最强的抗原递呈细胞,也是唯一能将抗原递呈给naiveT细胞、激发初次免疫应答的抗原递呈细胞,其在机体固有免疫以及适应性免疫中均发挥着重要的作用.支气管哮喘(简称哮喘)是一种常见的气道慢性炎症性疾病,存在Th1/Th2细胞亚群数量与功能失衡.近年来,研究显示,通过释放一系列的趋化因子以及细胞因子,DCs能活化naive T细胞并影响其极化,参与哮喘的发生发展.然而,不同DCs的亚型诱导naive T细胞极化的方向不尽相同,在决定机体对抗原是免疫耐受还是免疫反应发挥着不同作用.本文就DCs不同亚型在哮喘中的作用作一综述.     

树突状细胞在膀胱癌免疫治疗中的应用进展

膀胱肿瘤是泌尿系统最常见的肿瘤之一[1],治疗后容易复发。膀胱癌术后辅助治疗抑制肿瘤复发是膀胱癌治疗的重要组成部分。在机体对肿瘤细胞的免疫应答过程中,T细胞介导的免疫应答在机体抗肿瘤过程中起主导作用,但T细胞的致敏、激活和扩增均需依赖于抗原递呈细胞(APC)递呈相应的     

树突细胞与乙型肝炎病毒感染

树突状细胞(Dendritic Cells,DC)由美国学者Steinman及cohn于1973年发现,是体内重要的一类抗原递呈细胞(Antigen—presenting cells,APC),其共同的生物学特性是细胞表面有许多树枝状突起,胞内具有丰富的线粒体,与巨噬细胞、B细胞抗原递呈功能不同,只有DC能够刺激初始型T细胞(Naive T cells)使之分化、激活,后者影响机体的细胞和体液免疫系统,因此,DC被认为是机体免疫反应的始动者。     

树突状细胞在慢性阻塞性肺疾病发病过程中的作用

树突状细胞（dendrtic cells,DCs）是目前发现的体内功能最强的抗原递呈细胞（antigen presenting cells,APC）,在免疫应答中有着的独特的地位。越来越多的证据表明,呼吸道DCs不仅能诱导外界吸人抗原致敏,而且还能显著刺激初始型T细胞向Thl或Th2分化,而且在调节T细胞免疫应答、     

Antigen presentation in retroviral vector-mediated gene transfer in vivo

We have examined mechanisms involved in gene transfer, protein expression, and antigen presentation after direct administration of retroviral vectors using a variety of antigen systems. We have identified transduced infiltrating cells at the injection site, and the majority of the infiltrating cells were of the monocyte/macrophage lineage. We found that the splenic dendritic cell fraction contained proviral DNA, expressed antigenic proteins, and was able to present antigens efficiently to the immune system. Furthermore, the dendritic cell fractions from retroviral vector-immunized mice were able to prime naive T cells in vitro, and adoptive transfer of in vitro-transduced dendritic cell fractions elicited antigen-specific cytotoxic T lymphocytes. These data suggest a role for dendritic cells in induction of immune responses elicited by retroviral vector-mediated gene transfer.     

老年患者恶性胸水中肿瘤浸润免疫细胞体外活化

目的 观察老年患者恶性胸水中肿瘤浸润免疫细胞的活性.方法 分离恶性胸水单个核细胞(PEMCs),采用两步贴壁法,获得非贴壁细胞,树突细胞及淋巴细胞是其主要功能细胞成分.IL-2活化肿瘤浸润免疫细胞,SP法检测T淋巴细胞亚群的数量及免疫功能,SP法S-100蛋白染色检测树突细胞.结果 IL-2活化培养7 d后肿瘤浸润树突细胞(TIDC)和肿瘤浸润T淋巴细胞(TIL)数量明显增加(P<0.01).恶性胸水TIDC经过IL-2活化后具有抗原提呈功能.结论 IL-2活化肿瘤微环境中TIDC,使其恢复免疫监视功能,有效地负载肿瘤抗原,协同TIL等其他免疫细胞有效杀伤肿瘤细胞.     

Dendritic cell based genetic immunization stimulates potent tumor protection dependent on CD8 CTL cells in the absence of autoimmunity

Although antibodies (Abs) produced by B cells can treat cancer in certain models, T cells have been accountable for the major effector to control cancer. Immune recognition toward tyrosinase-related protein-1 (TRP-1), a melanoma associated antigen up-regulated on the surface of B16F10 melanomas, generally leads to tumor protection mediated by Abs. In this study, immunization with dendritic cells ex vivo transduced with adenovirus encoding TRP-1 stimulates immune activation and potent tumor protection mediated by CD8 T cells in the absence of autoimmune consequence. Transfer of CD8 T cells from immunized mice also leads to tumor protection. The immune activation and CD8 T cell mediated tumor protection rely on the CD4 T cell help. Thus DC based genetic immunization targeting TRP-1, an antigen usually causes Ab predominant immune recognition, is capable of stimulating potent tumor protection dependent on CD8 T cells in the absence of autoimmunity.     

Role of dendritic cells in progression and clinical outcome of colon cancer

Purpose  

The dendritic cells (DCs) are key players in the initiation and regulation of immune responses including antitumor immunity. In the current study, we aimed to elucidate the role of different subtypes of DCs infiltrating the tumor stroma and invasive margin for tumor progression and survival of patients with colon cancer.     

Morphological observation of tumor infiltrating immunocytes in human rectal cancer

AIM: To investigate the morphological characterization of tumor infiltrating dendritic cells (TIDCs) and tumor infiltrating lymphocytes (TILs) in human rectal cancer. METHODS: Light and electron microscopy as well as im-munohistochemistry were used to observe the distributive and morphological changes of TIDCs and TILs. RESULTS: TIDCs were mainly located in tumor-surrounding tissue. The number of TIDCs in the earlier stage was higher than that in the later stage (P<0.01). TILs were mainly seen in adjacent tissue of cancers and tumor-surrounding tissue. There were more TILs in the earlier stage than that in the later stage (P<0.01). Under electron microscope, TIDCs were irregular in shape and exhibited many dendritic protrusions. It isn't obvious that cancer cells perforated the basement membrane and TILs were arranged along the basement membrane in the earlier stage. In the later stage, it is explicit that cancer cells perforated the basement membrane and surrounded by TILs. There were contacts among TIDCs, TILs and tumor cell. One TIDCs contacted one or several TILs which clustered around TIDCs. Glycogen granules were seen between TIDCs and TILs. CONCLUSION: The number of TIDCs and TILs is related with tumor progression There exist close relationships among TIDCs, TILs and tumor cell.     

Dendritic cells: development, function and potential use for cancer immunotherapy

Dendritic cells (DC) are potent antigen presenting cells that are essential for the initiation of primary immune responses. They richly express MHC, costimulatory and adhesion molecules necessary for the stimulation of naive T cell populations. Dendritic cells are located at sites of antigen capture where they demonstrate phagocytic capacity and subsequently migrate to lymphatic areas for antigen presentation. Their phenotypic and functional characteristics are intimately linked to their stage of maturation. The hematopoietic development of dendritic cells is distinct and may follow several precursor pathways some closely linked to monocytes. Generation of large numbers of cells for potential clinical use has recently been accomplished through the in vitro culturing of progenitors with cytokines. The use of dendritic cell vaccines for cancer immunotherapy has emerged as an exciting new focus of investigation. Various strategies have been adopted to introduce tumor antigens into dendritic cells so that they may be more effectively presented to T cells in the context of costimulation. Animal models demonstrate that dendritic cell tumor vaccines reverse T-cell anergy and result in subsequent tumor rejection. Incorporating the expanding knowledge of dendritic cell biology into vaccine design is essential for the generation of effective immunotherapy for cancer patients.     

Gastrointestinal cancer stem cells as targets for innovative immunotherapy

The role of cancer stem cells in gastrointestinal cancer-associated death has been widely recognized. Gastrointestinal cancer stem cells(GCSCs) are considered to be responsible for tumor initiation, growth, resistance to cytotoxic therapies,recurrence and metastasis due to their unique properties. These properties make the current therapeutic trials against GCSCs ineffective. Moreover, recent studies have shown that targeting stem cell surface markers or stemness associated pathways might have an additional off-target effect on the immune system.Recent advances in oncology and precision medicine have opened alternative therapeutic strategies in the form of cancer immunotherapy. This approach differs from classical anti-cancer therapy through its mechanism of action involving the activation and use of a functional immune system against tumor cells, instead of aiming physically destruction of cancer cells through radio-or chemotherapy. New immunological approaches for GCSCs targeting involve the use of different immune cells and various immune mechanisms like targeting specific surface antigens, using innate immune cells like the natural killer and T cells, T-cell chimeric antigen receptor technology, dendritic cell vaccine, or immune checkpoint inhibitors. In this respect, better understandings of immune regulatory mechanisms that govern anti-tumor response bring new hope in obtaining long-term remission for cancer therapy.     

Heparanase expression, degradation of basement membrane and low degree of infiltration by immunocytes correlate with invasion and progression of human gastric cancer

AIM： To disclose the mechanisms that accelerate or limit tumor invasion and metastasis in gastric cancer patients. METHODS： The heparanase expression, continuity of basement, degree of infiltration by dendritic cells and lymphocytes in gastric cancer tissues from 33 the early and late stage patients were examined by immunohistochemistry, in situ hybridization and transmission electron microscopy. RESULTS： Heparanase mRNA expression in the late stage patients with gastric cancer was stronger than that in the early stage gastric cancer patients. In the early stage gastric cancer tissues, basement membrane （BM） appeared intact, whereas in the late stage, discontinuous BM was often present. The density of Sl00 protein positive tumor infiltrating dendritic cells （TIDC） in the early stage gastric cancer tissues was higher than that in the late stage. The infiltrating degree of tumor infiltrating lymphocytes （TIL） in the early stage patients whose tumor tissues contained a high density of TIDC was significantly higher than that in the late stage gastric cancer tissues patients with a low density of TIDC. There were few cancer cells penetrated through the continuous BM of cancer nests in the early stage gastric cancers, but many cancer cells were found outside of the defective BM of cancer nests in the late stage. CONCLUSION： Our results suggest that strongheparanase expression is related with the degradation of BM which allows or accelerates tumor invasion and metastasis. However, high density of TIDC and degree of infiltration by TIL are associated with tumor progression in human gastric cancers.     

Role of tyrosine kinase inhibitors in tumor immunology

Various immune cells are involved in both innate and acquired immunity against tumors. NK cells and cytotoxic T lymphocytes play a role as effector cells to directly kill tumor cells. On the other hand, antigen-presenting cells, particularly dendritic cells, control tumor-specific immune responses. In addition, much focus has been paid on the immune regulatory cells in tumor sites, including CD4(+)CD25(+) regulatory T cells and myeloid-derived suppressor cells. The recent advances in molecular-targeted therapy for cancer have provided small-molecule kinase inhibitors, which are effective for several hematopoietic malignancies as well as solid tumors in the clinical setting. Most drugs generally have inhibitory effects on several kinases, including tyrosine kinases, which are critical molecules for the survival, proliferation, migration and invasion of tumor cells. Since the host immune surveillance against tumors affects tumor progression, it is of interest to understand how these molecular-targeted drugs affect immune function in the tumor-bearing host. Besides this, there are emerging findings that myeloid cells could be involved in tumor angiogenesis. In this article, we address the role of tyrosine kinase inhibitors in tumor immunology by summarizing their effects on myeloid cells, such as antigen-presenting cells and regulatory cells, and their role in tumor immunity and angiogenesis.     

Expression of programmed cell death 1 and programmed cell death ligand 1 in extranodal NK/T-cell lymphoma,nasal type

Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) are new therapeutic targets in cancer immunotherapy. The aim of this study was to investigate the clinicopathological characteristics of PD-1 and PD-L1 expression in extranodal natural killer/T?cell lymphoma, nasal type (ENKTL). We performed PD-1 and PD-L1 immunostaining in 79 ENKTL biopsy samples and retrospectively analyzed medical records of all 79 patients from four tertiary referral hospitals. The expression of PD-1 and PD-L1 by tumor cells and/or infiltrating immune cells was evaluated. The expression rates of PD-L1 in tumor cells and infiltrating immune cells were 79.7 and 78.5 %, respectively, whereas PD-1 in tumor cells and infiltrating immune cells were 1.3 and 11.4 %. The PD-L1 positivity in tumor cells and infiltrating immune cells was significantly associated with low international prognostic index (IPI) (P?=?0.044 and 0.037, respectively). Patients with normal range of serum lactate dehydrogenase demonstrated a significantly higher PD-L1 positivity in tumor cells (P?=?0.020). PD-L1-positive patients had a trend toward better overall survival compared with that in patients with PD-L1-negative in tumor cells and infiltrating immune cells (P?=?0.498 and 0.435, respectively). The expression rate of PD-L1 was up to 79.7 % in ENKTL, while PD-1 expression rate was very low. This is the first report describing the clinicopathological features and survival outcome according to expression of PD-1 and PD-L1 in ENKTL.