共查询到19条相似文献,搜索用时 343 毫秒
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肿瘤细胞能够通过多种机制抵御免疫防御或药物的抗肿瘤作用.近年研究发现,外泌体能够直接介导癌症的进展和远端转移灶的形成.更为重要的是,在肿瘤免疫微环境中,肿瘤来源外泌体不仅能够抑制树突状细胞(DC)、巨噬细胞、T细胞、NK细胞等免疫细胞功能,还能促进骨髓来源的抑制性细胞(MDSC)、调节性T细胞(Treg)等的免疫抑制功能,进而降低抗肿瘤免疫应答过程,帮助肿瘤细胞逃避机体免疫细胞识别.本文将概述肿瘤外泌体及其携带的关键介质分子在介导肿瘤免疫逃逸和耐受过程中扮演的角色,并对这一研究领域的最新进展作一综述. 相似文献
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树突细胞特异性细胞间黏附分子-3-结合非整合素分子(DC-SIGN)首先是在DC表面发现的II型跨膜凝集素受体,能够与细胞间黏附因子2(ICAM-2)和ICAM-3结合,并能识别结合富含甘露糖的碳水化合物和含岩藻糖的多糖结构(如Lex,Ley,Lea及Leb)等病原相关分子模式,一方面可以通过受体介导的内吞、摄取、处理、提呈可溶性抗原,诱发机体对病原体的免疫应答;另一方面DC-SIGN诱发的信号通路能下调宿主免疫应答,导致病原体扩散、传播、免疫抑制和持续性感染。近年来,人们通过对许多病原体的免疫逃逸现象进行的大量研究工作,发现DC-SIGN与病毒的糖蛋白、细菌和真菌的荚膜多糖(CPS)等结合,使病原体藏匿于DC细胞而逃避溶酶体的降解,促进病原体传播实现免疫逃逸。 相似文献
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肿瘤在发生发展过程中会产生异常糖基化结构,改变细胞功能,使其能逃逸机体细胞的免疫识别和免疫攻击,实现免疫逃逸。细胞膜表面蛋白的N-糖基化参与调控肿瘤细胞的增殖、迁移、侵袭、干细胞特性等。近年来,一系列研究进一步证实,肿瘤细胞免疫检查点分子的N-糖基化,以及识别N-糖基化的动物凝集素在肿瘤免疫逃逸CD8+T细胞中发挥了重要作用,如PD-L1的N-糖基化能增强其自身蛋白质的稳定性,促进与其受体PD-1的相互作用,并且靶向PD-1、PD-L1蛋白N-糖基化的抗体,能够有效抑制肿瘤免疫逃逸和肿瘤发展。 相似文献
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《微生物学免疫学进展》2016,(3)
EB病毒(Epstein-Barr vius,EBV)是一种最广泛的对人类感染的γ疱疹病毒,与人类多种疾病尤其是恶性肿瘤有关。其致病的一个重要条件是能够在人体B细胞中长期潜伏,并且在人体免疫力低下时被激活并增殖,这表明EB病毒存在逃逸宿主细胞免疫的机制。从潜伏期EB病毒基因表达的下调、干扰抗原加工和提呈、调节细胞毒性T细胞(Cytotoxic lymphocyte,CTL)免疫应答、干扰细胞因子的作用、干扰CTL的活动及抑制宿主细胞凋亡、抑制辅助性T细胞1(Helper T cell 1,Th1)免疫应答等方面,对EB病毒免疫逃逸的分子机制作一简要综述。 相似文献
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耗竭性T细胞(exhausted T cells)是一群效应功能减弱,持续表达抑制性受体的T细胞,在肿瘤中表现为T细胞功能缺陷状态,主要特征为一系列抑制性受体表达增加及细胞因子分泌减少。耗竭性T细胞主要通过细胞表面的抑制性分子,细胞因子和免疫调节细胞类型改变等参与肿瘤免疫负调控,从而引起肿瘤免疫逃逸。而T细胞耗竭状态并非不可逆转,应用相应单克隆抗体靶向免疫调控点可以有效逆转耗竭性T细胞,恢复机体抗肿瘤免疫反应,提高肿瘤控制率。因此,通过逆转肿瘤患者体内的耗竭性T细胞可能是肿瘤免疫治疗的新途径之一。 相似文献
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阻断免疫检查点分子的信号通路可以增强免疫系统功能,这在肿瘤治疗中获得了显著效果。乙型肝炎病毒(Hepatitis B virus,HBV)慢性感染的原因之一为HBV在体内通过一系列方式来减弱、抑制免疫系统的功能,从而逃避免疫识别和杀伤。HBV可以通过上调病毒特异性T细胞表面的抑制性受体来抑制T细胞活化、增殖和效应。本文总结了HBV导致的人体内T细胞上免疫检查点程序性死亡受体1(Programmed cell death protein 1,PD-1)、细胞毒T淋巴细胞相关抗原4(Cytotoxic T-lymphocyte-associated protein 4,CTLA-4)、T细胞免疫球蛋白黏蛋白3(T-cell immunoglobulin domain and mucin domain-containing molecule-3,Tim-3)、淋巴细胞活化基因3(Lymphocyte-activation gene 3,LAG-3)、T细胞免疫球蛋白和免疫受体酪氨酸抑制基序(T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain,TIGIT)的异常表达以及它们影响T细胞功能的机制,揭示了免疫检查点在治疗慢性乙肝中的良好应用前景。 相似文献
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Gutzmer R Li W Sutterwala S Lemos MP Elizalde JI Urtishak SL Behrens EM Rivers PM Schlienger K Laufer TM Eck SL Marks MS 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(2):1023-1032
Tumors evade immune surveillance despite the frequent expression of tumor-associated Ags (TAA). Tumor cells escape recognition by CD8(+) T cells through several mechanisms, including down-regulation of MHC class I molecules and associated Ag-processing machinery. However, although it is well accepted that optimal anti-tumor immune responses require tumor-reactive CD4(+) T cells, few studies have addressed how tumor cells evade CD4(+) T cell recognition. In this study, we show that a common TAA, GA733-2, and its murine orthologue, mouse epithelial glycoprotein (mEGP), function in blocking MHC class II-restricted Ag presentation by dendritic cells. GA733-2 is a common TAA that is expressed normally at low levels by some epithelial tissues and a subset of dendritic cells, but at high levels on colon, breast, lung, and some nonepithelial tumors. We show that ectopic expression of mEGP or GA733-2, respectively, in dendritic cells derived from murine bone marrow or human monocytes results in a dose-dependent inability to stimulate proliferation of Ag-specific or alloreactive CD4(+) T cells. Dendritic cells exposed to cell debris from tumors expressing mEGP are similarly compromised. Furthermore, mice immunized with dendritic cells expressing mEGP from a recombinant adenovirus vector exhibited a muted anti-adenovirus immune response. The inhibitory effect of mEGP was not due to down-regulation of functional MHC class II molecules or active suppression of T cells, and did not extend to T cell responses to superantigen. These results demonstrate a novel mechanism by which tumors may evade CD4(+) T cell-dependent immune responses through expression of a TAA. 相似文献
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Wolfgang H. Fischer Per thor Straten Patrick Terheyden Jürgen C. Becker 《Cancer immunology, immunotherapy : CII》1999,48(7):363-370
A major difficulty for tumor immunotherapy derives from the phenomenon that the encounter of the immune system with an antigen
does not necessarily result in activation, but may also be followed by the induction of tolerance either by anergy or physical
deletion. It is well established that the immune system becomes alerted only in the face of danger, i.e. upon ligand recognition
in the context of increased expression of costimulatory molecules, adhesion molecules, and MHC molecules on antigen-presenting
cells (APC). The pivotal role of CD4+ T lymphocytes in this process has been established. However, encounter of CD4+ T cells with either MHC class II-expressing melanoma cells or certain tumor antigen-presenting APC has been reported to induce
antigen-specific tolerance. Thus, as more is learned about the molecular regulation of immune responses and the role of CD4+ T cells in particular, additional strategies to block inhibitory pathways of T-cell activation will be developed. Such strategies
are likely to be based on a modulation of the context in which antigen is encountered by the immune system, e.g. in situ cytokine
therapy, induction of costimulatory molecules or the simulation of `danger' signals.
Received: 20 March 1999 / Accepted: 3 May 1999 相似文献
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自然杀伤细胞是机体固有免疫系统重要组成部分,在肝脏等免疫器官中含量丰富,而且免疫表型、功能等表现出器官特异性。在正常情况下,靶细胞表面的配体与自然杀伤细胞表面的活化性受体直接结合并释放细胞毒性物质,诱导活化靶细胞凋亡程序,从而发挥抗感染、抗肿瘤作用。然而肿瘤细胞仍能够通过多种途径逃逸机体的免疫监视功能,研究认为肿瘤细胞抗原异常表达、肿瘤微环境中细胞因子及其他免疫细胞相互作用等因素所引起的自然杀伤细胞活性降低对于诱导肿瘤免疫逃逸起重要作用。本文综述了自然杀伤细胞在肝脏恶性肿瘤发生过程中参与免疫逃逸的机制及研究进展,以期为临床抗肿瘤免疫治疗的研究提供参考。 相似文献
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Tumor cells act upon, and react to both their proximate and more distant environment, the mechanisms by which this is achieved
being both autocrine and paracrine in nature. This interaction, however, takes place not only between adjacent malignant cells,
but also non-malignant cells such as those of the immune system, the latter also partaking in the modeling of the tumor environment.
Although tumor cells descend from normal tissue cells and thus bear in classical immunological terms ‘self signals’, it is
evident that the immune system is able to recognize tumor cells as a harassment for the body and in consequence tries to eliminate
these cells. On the counterpart, tumor cells acquire various characteristics which allow them to evade this immunological
surveillance, and have been collectively coined with the term “tumor escape mechanisms”. This review will describe and summarize
current understanding of tumor escape strategies, and also more closely elaborate on the modulatory role of the neuroendocrine
system in the immune system–tumor cell interaction. 相似文献
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Tarazona R Casado JG Soto R DelaRosa O Peralbo E Rioja L Peña J Solana R 《Cancer immunology, immunotherapy : CII》2004,53(10):911-924
The coexistence of tumor progression with a tumor-specific immune response constitutes a major paradox of tumor immunity. During the last decade, the presence of cytotoxic T lymphocytes (CTLs) recognising melanoma-associated antigens has been unequivocally demonstrated in numerous different in vivo and in vitro models. However, most often these melanoma-specific T lymphocytes do not control tumor growth. Several mechanisms that involve changes in melanoma phenotype and/or in T-cell differentiation and function could explain the inability of the immune response to control melanoma. In the last few years it has been demonstrated that cellular cytotoxicity is the result of a balance between activating signals triggered by the TCR and costimulatory molecules and inhibitory signals triggered by inhibitory receptors expressed by the CTL. Because the final outcome of the immune response against melanoma depends on the balance between activating and inhibitory signals, the expression de novo on melanoma cells of ligands for inhibitory NKRs and the down-regulation of costimulatory molecules may favor the escape of tumor cells from immunosurveillance. In this paper we review how altered expression of molecules required for T-cell costimulation could result in impaired lysis of melanoma. The modulation of antimelanoma T-cell responses by a group of receptors originally described on NK cells (NK-associated receptors) but which are now known also to be expressed on a subset of cytolytic effector cells is reviewed. We hypothesize that the expression of ligands for NKRs on melanoma cells may contribute to T-cell-mediated immune responses against melanoma either enhancing or inhibiting activation and differentiation to effector cells. Blocking inhibitory receptors or increasing activating receptors could result in new strategies to improve T-cell-mediated rejection of melanoma. 相似文献
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The establishment of tumor escape mutants, which can be driven by innate and/or adaptive immune effector cells, presents a significant obstacle in the development of successful tumor immunotherapies. Our study documents that tumors growing within an immune-privileged site within the eye develop a tumor escape phenotype in the absence of selective T cell pressure. P815 tumor cells that are recovered from progressively growing tumors within the anterior chamber of the eye escape elimination when injected into the flanks of a second group of syngeneic DBA/2 mice that were previously immunized against P815 tumor cells. The escape phenotype of eye-derived P815 tumors was stable and permanent when the tumor cells were cultured in vitro. Eye-derived tumor cells recovered from the anterior chamber of CB-17 SCID mice also escaped elimination when injected into the flanks of immunized mice, demonstrating that selective pressure by tumor Ag-specific T cells did not contribute to the development of the escape phenotype. In vitro studies demonstrated that eye-derived tumor cells were not lysed by specific CTL and were unable to restimulate primed Ag-specific T cells. Immune escape of eye-derived tumor cells was not due to down-regulation of either MHC class I or ICAM-1. Our data demonstrate that the immune-privileged environment within the eye induces a tumor escape phenotype that is not driven by selective T cell pressure. We predict that immune escape within the eye is driven by the unique ocular environment that permanently alters gene expression in eye-derived tumor cells. 相似文献
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The revived cancer immune surveillance theory has emphasized the active role the immune system plays in eliminating tumor cells and in facilitating the emergence of their immunoresistant variants. MHC class I molecule abnormalities represent, at least in part, the molecular phenotype of these escape variants, given the crucial role of MHC class I molecules in eliciting tumor antigen-specific T cell responses, the high frequency of HLA class I antigen abnormalities in malignant lesions and their association with a poor clinical course of the disease. Here, we present evidence for this possibility and review the potential mechanisms by which T cell selective pressure participates in the generation of tumor cells with MHC class I molecule defects. Furthermore, we discuss the strategies to counteract tumor cell immune evasion. 相似文献
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To escape the immune system, tumor cells may remove surface molecules such as the major histocompatibility complex (MHC) and
co-stimulatory molecules, which are essential for recognition by lymphocytes. Down-regulation of the co-stimulatory molecules
CD70 (TNFSF7) and CD80 may contribute to tumor cell survival; however, the mechanism of down-regulation of the TNFSF7 gene during tumorigenesis is poorly understood. Here we present evidence indicating that TNFSF7 gene expression is epigenetically down-regulated via DNA hypermethylation within its promoter region during progression in
breast cancer cells in the isogenic MCF10 model. Bisulfite sequencing revealed that the CpG pairs at the proximal region of
the TNFSF7 promoter are heavily methylated during progression of breast cancer cells but that methylation of the more distal sequences
was not changed considerably. Thus, this epigenetic silencing of the TNFSF7 gene via hypermethylation of its proximal region may allow the benign and invasive MCF10 variants to escape immune surveillance. 相似文献
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Kowalczyk DW 《Acta biochimica Polonica》2002,49(2):295-302
This article reviews the evidence for the danger model in the context of immune response to tumors and the insufficiency of the immune system to eliminate tumor growth. Despite their potential immunogenicity tumors do not induce significant immune responses which could destroy malignant cells. According to the danger model, the immune surveillance system fails to detect tumor antigens because transformed cells do not send any danger signals which could activate dendritic cells and initiate an immune response. Instead, tumor cells or antigen presenting cells turn off the responding T cells and induce tolerance. The studies reviewed herein based on model tumor antigens, recombinant viral vectors and detection of tumor specific T cells by MHC/peptide tetramers underscore the critical role of tumor antigen presentation and the context in which it occurs. They indicate that antigen presentation only by activated but not by cancer or resting dendritic cells is necessary for the induction of immune responses to tumor antigens. It becomes apparent that the inability of dendritic cells to become activated provides a biological niche for tumor escape from immune destruction and seems to be a principal mechanism for the failure of tumor immune surveillance. 相似文献