调节性T细胞在结直肠癌免疫治疗中的意义

肿瘤微环境(TME)中的免疫抑制会减弱抗肿瘤免疫,从而阻碍机体的保护性免疫监视并阻止癌症免疫疗法诱导的有效抗肿瘤免疫。多种机制参与了TME的免疫抑制,其中包括多个免疫位点(如CTLA-4、PD-1和LAG-3)和免疫抑制细胞。调节性T (Treg)细胞是一类免疫抑制细胞,在抑制机体抗肿瘤免疫方面发挥着重要作用。TME中的Treg细胞与结直肠癌的不良预后密切相关。Treg细胞被认为是结直肠癌免疫治疗中主要靶点之一。因此,阐明癌症患者的Treg细胞功能对于开发最佳的Treg细胞靶向免疫疗法至关重要。本文就TME中的Treg细胞的功能和表型以及靶向免疫疗法中可能的治疗策略进行综述。     

人参皂甙的抗肿瘤作用及其机制

人参皂甙的抗肿瘤作用机制较为广泛，主要表现为直接作用于癌细胞，通过诱导细胞凋亡抑制肿瘤生长或诱导细胞分化使其逆转；作用于肿瘤侵袭的多个环节抑制其转移；逆转肿瘤的耐药性提高化疗药物的抗肿瘤活性；调节免疫功能增强机体抗肿瘤能力；影响细胞连接通讯或抑制酶的活性及拮抗致癌剂的作用等。     

表阿霉素对乳腺癌患者外周血中调节性T细胞数目的影响

<正>CD4+CD25+T细胞又称调节性T细胞(regulatory Tcell,Treg),是机体免疫系统的重要组成部分,在防止自身免疫、保持机体的自身耐受性中发挥着决定性作用。化疗药物对机体免疫系统有一定程度的杀伤或抑制效应,因而普遍认为化疗抑制了机体的免疫功能。但是新近的研究发现,某些化疗药物可以通过增强肿瘤细胞免疫原性,促进肿瘤细     

CD4+CD25+调节性T细胞在肿瘤免疫中的意义及研究进展

肿瘤的发生发展与宿主的免疫状态密切相关,宿主抗肿瘤反应以细胞免疫为主,多种肿瘤患者存在T淋巴细胞亚群状态异常和比例失调.CD4+CD25+调节性T细胞(Tregulatory cells,Treg)近年来引起国内外学者的广泛关注,越来越多的研究表明,Treg参与肿瘤的免疫逃逸,使肿瘤特异性T效应细胞不能扩增到一定水平以根除肿瘤[1,2].现将CD4+CD25+Treg在肿瘤免疫中的意义及研究进展综述如下.     

CD4~+CD25~+调节性T细胞在肿瘤免疫中的意义及研究进展

肿瘤的发生发展与宿主的免疫状态密切相关,宿主抗肿瘤反应以细胞免疫为主,多种肿瘤患者存在T淋巴细胞亚群状态异常和比例失调.CD4 CD25 调节性T细胞(Tregulatory cells,Treg)近年来引起国内外学者的广泛关注,越来越多的研究表明,Treg参与肿瘤的免疫逃逸,使肿瘤特异性T效应细胞不能扩增到一定水平以根除肿瘤[1,2].现将CD4 CD25 Treg在肿瘤免疫中的意义及研究进展综述如下.     

肿瘤免疫逃逸相关分子及其机制研究进展

肿瘤细胞可通过多种途径逃避机体的免疫杀伤作用,如异常表达肿瘤表面抗原,改变细胞表面分子结构,或利用Fas/FasL(Fas ligand)系统分泌免疫抑制因子等抑制肿瘤免疫反应等。此外,不同种类的活化免疫细胞如自然杀伤(NK)细胞、调节性T细胞(Treg)、肿瘤相关巨噬细胞(TAM)、髓系抑制细胞(MDSC)、缺氧诱导因子1(HIF-1)、B7-H4等在肿瘤免疫逃逸过程中也扮演重要角色。NK细胞作为监视屏障、Treg抑制免疫细胞的活性并分泌免疫抑制细胞因子转化生长因子TGF-β(TGF-β)和白介素-10(IL-10)等、TAM降解细胞外基质,增加血管通透性,促进肿瘤细胞侵袭和迁移、HIF-1调控血管内皮生长因子(VEGF)的产生,促进内皮细胞增殖,促进新生血管出芽等。本文对近年来不同种类活化免疫细胞参与肿瘤免疫逃逸机制的研究进展做一综述。     

Treg细胞对肿瘤微环境的作用研究进展

调节性T细胞(Treg细胞)在肿瘤微环境(TME)中具有免疫负调节功能,下调抗肿瘤免疫,为肿瘤微环境免疫治疗研究的靶点.Treg细胞对肿瘤微环境的作用包括对代谢及相关信号通路调节.其中包括IL-33/ST2通路、PI3K通路、Hippo通路与Wnt/β-catenin通路.通过研究Treg细胞对肿瘤微环境的调节作用可以...     

肺肿瘤小鼠MDSC、 Treg 及传统T 细胞变化研究

摘要： 目的 探讨肺肿瘤小鼠骨髓源性抑制细胞 （MDSC）、 调节性 T 细胞 （Treg） 和传统 T 细胞的变化及机制。方法 采用配对设计将 20 只 C57BL/6 小鼠随机均分为 Lewis 肺癌细胞注射组 （LLC 组） 和正常对照组 （NC 组）, LLC 组采用皮下注射 LLC 细胞 100 μL （1×106 ） 制备肺肿瘤小鼠模型, 对照组注射等量生理盐水。待肿瘤形成后取小鼠脾细胞, 采用流式细胞仪检测肺肿瘤小鼠 MDSC、 Treg 及 CD4+ 和 CD8+ T 细胞比例和数量变化, 膜联蛋白-V （Annexin-Ⅴ）染色检测 CD4+ 和 CD8+ T 细胞凋亡变化, 5-溴脱氧尿嘧啶核苷 （BrdU） 染色检测 CD4+ 和 CD8+ T 细胞增殖变化。结果 与 NC 组相比, LLC 组脾脏 MDSC 比例和数量明显增加, CD4+ Foxp3+ Treg 所占 CD4+ T 细胞比例和数量明显增加,而 CD4+ 和 CD8+ T 细胞所占脾细胞比例和数量明显降低 （均 P < 0.05）。与 NC 组相比, LLC 组 CD4+ 和 CD8+ T 细胞增殖明显降低, 同时 CD8+ T 细胞凋亡明显增加 （P < 0.05）。结论 MDSC 和 Treg 细胞在肺肿瘤小鼠数量增加, 同时, MDSC 和Treg 抑制 CD4+ 和CD8+ T 细胞增殖, 并促进 CD8+ T 细胞凋亡。     

NK细胞的抗肿瘤机制及其在肿瘤靶向治疗中的应用研究进展

自然杀伤(natural killer, NK)细胞是固有免疫的重要组成部分,可通过表面抑制性受体与激活性受体的协同作用活化后,直接识别杀伤肿瘤细胞;可分泌细胞因子募集树突状细胞(dendritic cells, DCs),促进DCs成熟,增强适应性免疫应答;可杀伤肿瘤干细胞(cancer stem cells, CSCs)与循环肿瘤细胞(circulating tumor cells, CTCs),维持肿瘤细胞休眠,抑制肿瘤转移。NK细胞具备独特的炎症趋向性,可响应肿瘤部位释放的细胞因子与趋化因子迁徙至肿瘤部位,使其在抗肿瘤靶向治疗中占据重要优势。因此, NK细胞载体、NK细胞膜包被仿生化载体和NK细胞外囊泡(NK cell extracellular vesicles, NKEVs)的肿瘤靶向治疗研究,受到越来越多的关注。本文将重点介绍NK细胞抗肿瘤作用机制及其在肿瘤靶向治疗中的应用研究进展。     

复方参芪冲剂抗肿瘤作用

目的观察复方参芪冲剂对小鼠S180、H22、Lewis肿瘤生长及与化疗药物阿霉素(ADM)、顺铂(DDP)、环磷酰胺(CTX)合用对抗肿瘤活性和免疫功能的影响。方法采用动物移植瘤S180、H22、Lewis模型 ,对复方参芪冲剂的抗肿瘤作用及对化疗药物的增效减毒作用进行检测。结果复方参芪冲剂对小鼠S180、H22、Lewis均有明显抑制作用 ,明显增强ADM、DDP、CTX的抗肿瘤活性 ,对其所引起的免疫抑制性有明显保护作用。结论复方参芪冲剂的抗肿瘤作用及对化疗药物的增效解毒作用 ,可能是通过增强机体的免疫功能实现的     

Learning from Viruses: The Necrotic Bodies of Tumor Cells with Intracellular Synthetic dsRNA Induced Strong Anti-tumor Immune Responses

Purpose Coaxing dead tumor cells to induce specific immune responses is an attractive tumor therapy. However, there continues to be a need for adjuvants that can promote the cross-presentation of the dead tumor cells to induce specific anti-tumor response. Viral dsRNA has multiple mechanisms to promote the cross-presentation of viral antigens in virus-infected cells. We propose to learn from viruses by generating dead tumor cells having synthetic dsRNA delivered inside them to allow the dsRNA to promote the cross-presentation of dead tumor cells. Materials and Methods Using synthetic dsRNA, poly(I:C), and the TC-1 cervical cancer model, we evaluated the extent to which the poly(I:C) can promote the necrotic bodies of TC-1 cells to induce specific anti-tumor immune response. The poly(I:C) was either simply mixed with the dead TC-1 cells or pre-loaded inside them. Results Immunization of tumor-bearing mice with the necrotic bodies of tumor cells admixed with poly(I:C) significantly inhibited the tumor growth. More importantly, immunization with the necrotic bodies having poly(I:C) pre-loaded inside led to a significantly stronger anti-tumor response than when the necrotic bodies were simply admixed with the poly(I:C), apparently through a CD8⁺ CTL response-mediated mechanism. Conclusions These findings are expected to be clinically relevant for devising improved whole cell-based tumor vaccines.     

聚糖在肿瘤转移、免疫调节和治疗中的特定作用

聚糖与糖基化修饰对调节细胞功能至关重要,异常的糖基化修饰和聚糖含量或组成的改变可加速癌细胞的恶性转化,促进肿瘤转移并参与调节机体的抗肿瘤免疫反应,最终促进肿瘤发展.因此,研究肿瘤细胞相关糖基化和聚糖的异常表达对了解肿瘤的发生发展具有重要意义.本文旨在阐明糖基化和聚糖改变与肿瘤进展之间的密切联系并总结相关最新糖基化治疗策...     

Allograft-induced proliferation of vascular smooth muscle cells: potential targets for treating transplant vasculopathy

Despite advances in immunosuppressive drugs, coronary artery transplant vasculopathy (CATV) is the major cause of graft failure that limits long-term survival of cardiac transplantation. The pathogenesis of CATV involves a chronic immune response of the recipient to the donor vasculature in which activated recipient immune cells damage the endothelium and produce cytokines, resulting in vascular smooth muscle cell (VSMC) activation. Activated VSMC migrate from the media into the lumen, proliferate, and elaborate cytokines and matrix proteins, resulting in loss of lumen diameter and vascular contractility. Because of its extensive nature, interventions which are successful in patients with conventional coronary artery disease are often not applicable to the majority of patients with CATV. Although intended for immune suppression, many immunosuppressive agents owe at least part of their efficacy to their anti proliferative effects on VSMC, including rapamycin, mycophenolic acid, cyclosporin, calcium channel blockers, and HMG CoA reductase inhibitors. Because activation of VSMC is responsible for most of the obliterative arterial intimal thickening present in solid organ allografts, the induction of expression of a selected set of genes may reflect the status of acceptance of the vasculature by the recipient, and the activation, migration, and proliferation of VSMC represent potential points for therapeutic intervention. The risk of infection and malignancy associated with immunosuppressive therapy further promote the need to identify a molecular target which directly modulates the VSMC response to injury. This review will summarize the anti proliferative effects that immunosuppressive drugs have on VSMC proliferation. We will also describe efforts to define the genes which regulate the vascular response to allograft injury, and describe how some of these proteins may represent targets to reduce VSMC proliferation and attenuate CATV.     

Cellular therapy for ovarian cancer: experimental and clinical perspectives

Ovarian cancer is the leading cause of death among gynecologic malignancies and the 5th leading cause of cancer deaths for women in the United States. Two-thirds of patients present with advanced-stage disease (Stage III and IV) and the majority will suffer recurrence of disease, require ongoing treatment, and eventually succumb to chemotherapy-resistant disease. To potentially circumvent chemo-resistance in recurrent ovarian cancer, immunotherapy is being explored as a novel treatment option. Our laboratory findings demonstrate that immune effector cells from healthy donors elicit a significant cytotoxic response in the presence of IL-2 and IFN alpha- 2b against ovarian cancer in vitro; however, peripheral blood mononuclear cells (PBMC) isolated from ovarian cancer patients fail to elicit a similar response. A major obstacle to immunotherapy is the immunosuppressive environment supported by tumors, which limits the immune system's ability to fight the tumor. Myeloid-derived suppressor cells are an immature population of myeloid cells, which have recently been implicated to play a major role in immunosuppression and tumor evasion. In addition to novel immunotherapies, new diagnostic and prognostic markers are being identified through applying molecular tools/approaches in clinical and pathological analyses of this malignancy, which will provide additional therapeutic targets. To test these experimental therapeutic options, pre-clinical murine models of ovarian cancer are being developed. Ultimately, treatment of ovarian cancer will benefit from the careful alignment of appropriate target, drug, patient, and trial design. This article provides an objective overview of cellular therapy (the use of immune cells to elicit an anti-tumor response) for ovarian cancer highlighting both experimental and clinical perspectives.     

髓系抑制性细胞在肝癌发病中的作用研究进展

髓系抑制性细胞（MDSCs）是备受关注的免疫抑制性细胞,具有调节免疫应答的作用。近年发现MDSCs与肝癌发生发展及预后密切相关,肝癌微环境中多种因子影响MDSCs的扩增、活化和募集,而MDSCs通过下调机体的抗肿瘤免疫应答或诱导免疫耐受形成,促进肿瘤的生长与转移。研究MDSCs在肝癌免疫逃逸的作用,将为肝癌早期发现、诊断及免疫治疗等提供新线索。     

Targeted nanomedicines remodeling immunosuppressive tumor microenvironment for enhanced cancer immunotherapy

Cancer immunotherapy has significantly flourished and revolutionized the limited conventional tumor therapies, on account of its good safety and long-term memory ability. Discouragingly, low patient response rates and potential immune-related side effects make it rather challenging to literally bring immunotherapy from bench to bedside. However, it has become evident that, although the immunosuppressive tumor microenvironment (TME) plays a pivotal role in facilitating tumor progression and metastasis, it also provides various potential targets for remodeling the immunosuppressive TME, which can consequently bolster the effectiveness of antitumor response and tumor suppression. Additionally, the particular characteristics of TME, in turn, can be exploited as avenues for designing diverse precise targeting nanomedicines. In general, it is of urgent necessity to deliver nanomedicines for remodeling the immunosuppressive TME, thus improving the therapeutic outcomes and clinical translation prospects of immunotherapy. Herein, we will illustrate several formation mechanisms of immunosuppressive TME. More importantly, a variety of strategies concerning remodeling immunosuppressive TME and strengthening patients' immune systems, will be reviewed. Ultimately, we will discuss the existing obstacles and future perspectives in the development of antitumor immunotherapy. Hopefully, the thriving bloom of immunotherapy will bring vibrancy to further exploration of comprehensive cancer treatment.     

免疫细胞在脓毒血症中的作用及机制研究进展

脓毒血症是由危及生命的感染所引起的宿主炎症反应,伴随着严重的器官功能衰竭和障碍。近年来,尽管医学和医疗技术都取得了巨大进步,脓毒血症的病死率仍高达30%~70%。脓毒血症本质上是机体对感染性因素的反应,初始免疫反应是一种过度炎症状态,随后迅速发展为免疫抑制状态。了解参与脓毒血症期间器官损伤发展中的宿主细胞介导的免疫反应是至关重要的。总结了各类免疫细胞在人和小鼠脓毒血症期间的作用变化及机制研究进展。     

Fucoidan-functionalized activated platelet-hitchhiking micelles simultaneously track tumor cells and remodel the immunosuppressive microenvironment for efficient metastatic cancer treatment

Tumor metastasis is responsible for most mortality in cancer patients, and remains a challenge in clinical cancer treatment. Platelets can be recruited and activated by tumor cells, then adhere to circulating tumor cells (CTCs) and assist tumor cells extravasate in distant organs. Therefore, nanoparticles specially hitchhiking on activated platelets are considered to have excellent targeting ability for primary tumor, CTCs and metastasis in distant organs. However, the activated tumor-homing platelets will release transforming growth factor-β (TGF-β), which promotes tumor metastasis and forms immunosuppressive microenvironment. Therefore, a multitalent strategy is needed to balance the accurate tumor tracking and alleviate the immunosuppressive signals. In this study, a fucoidan-functionalized micelle (FD/DOX) was constructed, which could efficiently adhere to activated platelets through P-selectin. Compared with the micelle without P-selectin targeting effect, FD/DOX had increased distribution in both tumor tissue and metastasis niche, and exhibited excellent anti-tumor and anti-metastasis efficacy on 4T1 spontaneous metastasis model. In addition, due to the contribution of fucoidan, FD/DOX treatment was confirmed to inhibit the expression of TGF-β, thereby stimulating anti-tumor immune response and reversing the immunosuppressive microenvironment. The fucoidan-functionalized activated platelets-hitchhiking micelle was promising for the metastatic cancer treatment.