趋化因子与肺癌

趋化因子是一类趋化细胞定向移动的小分子蛋白,在肺癌中,趋化因子参与调节肿瘤细胞的生长、肿瘤内血管生成、抗肿瘤免疫及诱导远处转移的过程。趋化因子参与了肺癌进展,为肺癌的治疗提供了新的靶点。     

趋化因子与肺癌

趋化因子是一类趋化细胞定向移动的小分子蛋白,在肺癌中,趋化因子参与调节肿瘤细胞的生长、肿瘤内血管生成、抗肿瘤免疫及诱导远处转移的过程.趋化因子参与了肺癌进展,为肺癌的治疗提供了新的靶点.     

CXCL12／CXCR4生物轴与消化系统恶性肿瘤

消化系统恶性肿瘤发病率及死亡率均远远高于其它系统恶性肿瘤，对消化系统恶性肿瘤的预防和治疗研究亟待进一步深入。细胞移位是相当多病理生理过程的基本步骤，包括恶性肿瘤细胞的生长及转移。越来越多地研究认为肿瘤细胞通过化学趋化因子及其相应受体介导的化学趋化机制调节其生长和转移，趋化因子在恶性肿瘤中具有多方面作用，归纳为：①诱导白细胞向肿瘤组织浸润，调节免疫功能，尤其是肿瘤相关的巨噬细胞、T细胞和树突状细胞；②引导肿瘤细胞迁移到特定部位；③调节血管生成；④直接活化肿瘤细胞，调控其恶性肿瘤相关的功能表现。近年研究发现，趋化因子CXCL12及其受体CXCR4构成的生物轴在包括乳腺癌在内的多种实体瘤的生长、转移中发挥重要作用。CXCL12／CXCR4生物轴与消化系统恶性肿瘤之间关系密切，CXCL12的刺激促进CXCR4的表达及消化系统恶性肿瘤的转移；CXCR4持续高表达预示肿瘤的复发及预后不良；在CXCL12作用下，肿瘤细胞黏附／迁移和增殖能力亦显著增强，这些效应被CXCR4的抗体所拮抗。未来研究寄希望通过拮抗影响肿瘤转移的CXCL12与CXCR4等趋化因子及其受体的作用来阻断消化系统恶性肿瘤转移，将可能会成为一种新的治疗消化系统恶性肿瘤的有效途径。     

趋化因子及其受体在机体免疫调控中的作用

趋化因子(chemokines)是一类引起炎症反应或白细胞转移的细胞因子。近年来，趋化因子家族、趋化因子受体、趋化因子与疾病关系的研究已成为研究者们瞩目的热点。趋化因子及其受体与许多病理过程如HIV感染、炎症、自身免疫性疾病等有密切关系，在肿瘤生长、侵袭、转移过程中发挥关键作用，同时在免疫细胞的分化、发育和免疫应答的调控中起着重要作用。本文主要介绍趋化因子及其受体的结构和功能特点；趋化因子及     

中医药在肿瘤免疫治疗及相关不良反应中应用的研究进展

恶性肿瘤严重威胁人类生命健康,其发生发展与机体免疫功能息息相关。随着肿瘤免疫学的发展,免疫治疗成为继手术、放化疗及靶向治疗后又一治疗手段。相比于传统治疗方式,肿瘤免疫治疗能显著延长患者的生存期,但在治疗过程中仍可出现皮肤、胃肠道毒性等免疫相关不良反应。中医药是肿瘤综合治疗中不可或缺的一部分,其可参与抗肿瘤治疗的全过程。研究发现中医与肿瘤免疫关系密切,其通过调节机体免疫功能或肿瘤免疫微环境来调控肿瘤免疫,在缓解免疫相关不良反应方面也有一定的疗效。现就中医与肿瘤免疫的关系、中医药调节肿瘤免疫及常见免疫相关不良反应方面的研究进展作一综述。     

乳腺癌微环境中趋化因子CCL20作用的研究进展

趋化因子是一类低分子量细胞因子,在调节肿瘤微环境中发挥重要作用。肿瘤微环境中的趋化因子不仅能够趋化白细胞,也能诱导附近的反应细胞影响肿瘤生长、侵袭、转移和血管生成。趋化因子与炎症和肿瘤疾病的发生发展密切相关,其中CC家族中的趋化因子CCL20在多种恶性肿瘤的侵袭和转移中发挥重要作用。近年发现,趋化因子CCL20在乳腺癌免疫抑制、血管生成及诱导上皮间质转化和肿瘤侵袭转移中起重要的调控作用。然而,CCL20在乳腺癌中的作用机制尚未明确。本文重点阐述趋化因子CC亚家族成员CCL20在乳腺癌微环境中的功能,探讨CCL20与乳腺癌微环境之间的关系,以期为乳腺癌靶向治疗提供新的思路。     

脑胶质瘤中CXC趋化因子表达的预后意义及免疫细胞浸润分析

目的 分析多形性胶质母细胞瘤（GBM）中CXC趋化因子的表达,研究其在GBM中的预后价值及其作为治疗靶点的潜在作用。方法 利用GEPIA数据库筛选出差异表达的CXC趋化因子,并分析CXC趋化因子对GBM患者预后的影响。使用String数据库预测邻近基因,并构建蛋白互作网络（PPI）。使用DAVID数据库进行GO富集分析和KEGG通路富集分析。使用TRRUST和LinkedOmics预测转录因子和激酶靶标。使用TIMER分析差异表达趋化因子与肿瘤纯度和免疫细胞浸润程度的相关性。结果 CXCL2/3/8/9/10/11/16在GBM中的表达显著上调,其中CXCL3/8与患者不良预后显著相关。差异表达趋化因子及其邻近基因主要富集于免疫调控和细胞凋亡的功能和信号通路。趋化因子的表达与六种免疫细胞的浸润水平存在相关性。结论 CXCL3/8可作为GBM患者潜在的预后标志物。CXC趋化因子与GBM肿瘤免疫有关。     

肿瘤微环境对NK细胞功能调节的研究进展

自然杀伤(natural killer,NK)细胞作为固有免疫细胞成员之一,不仅能够通过细胞毒作用直接杀伤肿瘤细胞,还可通过释放细胞因子(如趋化因子)调节多种免疫细胞的功能,支持机体后续的适应性免疫应答.然而肿瘤细胞会通过多种机制成功规避NK细胞的识别,肿瘤微环境还能诱导多种免疫细胞功能异常,如髓系来源的抑制细胞(myeloid derived suppressorcells,MDSCs)、M2型肿瘤相关巨噬细胞(M2-tumor-associated macrophage,M2-TAM)、树突状细胞(dendritic cells,DCs)和调节性T细胞(regulatory T cells,Treg)等,通过干扰NK细胞活化相关信号通路或者受体表达,抑制NK细胞的活化和抗肿瘤活性,造成肿瘤免疫逃逸.本文从NK细胞的视角,在讨论NK细胞功能的转录调控机制同时,重点综述肿瘤微环境中多种类型细胞对NK细胞功能调节的最新研究进展.     

红细胞趋化因子受体在抗肿瘤免疫反应中的作用

红细胞趋化因子受体是一个G蛋白非偶联的杂性趋化因子受体,可作为趋化因子"清除槽"或诱骗受体,吸附肿瘤局部过多的血管生成性趋化因子,使肿瘤血管生成减少,阻止肿瘤生长和转移.肿瘤患者红细胞趋化因子受体活性有明显下降,使肿瘤局部免疫状态低下,利于肿瘤细胞生长和转移.     

肿瘤免疫中Treg细胞与趋化因子及受体的研究进展

近年来的研究发现,趋化因子系统和调节性T细胞在肿瘤发生、发展及转移中发挥重要作用。作为一种免疫抑制性调节细胞,CD4+CD25+调节性T细胞(regulatory T cells,以下简称Treg细胞)在体内通过多种途径发挥抑制效应性T细胞增殖,在诱导机体对肿瘤的免疫耐受和免疫逃逸中发挥关键作用。肿瘤可以通过多种途径来引导调节性T细胞在肿瘤局部的聚集和维持,其中最重要的一种方式为肿瘤细胞表面高表达趋化因子。现将近年来国内外对趋化因子及受体(特别是趋化因子受体5)与Treg细胞关系的研究进行综述。     

趋化因子与肺癌

趋化因子与其相应的受体作用,广泛参与生物活动及病理过程。研究发现多种肿瘤细胞都过表达功能性的趋化因子。在肺癌中,趋化因子参与了其增殖、凋亡、侵袭和转移等过程。肺癌过表达的趋化因子及其受体,可作为明确的靶向目标进行针对性的抗肿瘤治疗。     

Chemokine signaling in cancer: One hump or two?

Chemokines and their receptors play essential roles in the development and function of multiple tissues. Chemokine expression, particularly CXCL12 and its receptor CXCR4, has prognostic significance in several cancers apparently due to chemokine mediated growth and metastatic spread. These observations provide the rationale for pursuing CXCR4 inhibition for cancer chemotherapy. However, the multiple homeostatic functions of CXCR4 may preclude global inhibition as a therapeutic strategy. Here I review CXCR4 signaling and how it might differ in normal and transformed cells with special emphasis on the role that altered CXCR4 counter-regulation might play in tumor biology. I propose that CXCR4 mediates unique signals in cancer cells as a consequence of abnormal counter-regulation and that this results in novel biological responses. The importance of testing this hypothesis lies in the possibility that targeting abnormal CXCR4 signaling might provide an anti-tumor effect without disturbing normal CXCR4 functions.     

Melanoma and innate immunity – Active inflammation or just erroneous attraction?: Melanoma as the source of leukocyte-attracting chemokines

Unwanted growth breeds response – in the garden as well as in the tumor microenvironment. Innate immune cells mediate the earliest responses against melanoma or its precursors. However, the actual benefit by those cellular efforts is questionable. Why can early melanoma lesions actually develop in the face of rapid innate responses, and why is neutrophil- and macrophage-attracting chemokine secretion observed in melanoma?A surprisingly similar choice of chemokine receptors and chemokines are present in both innate immune cells and melanoma. Here we focus on analogies and differences between the two. Melanoma cell clusters show active chemokine signalling, with mostly tumor growth-enhancing and leukocyte-attracting effects. However, infiltrating leukocytes have only weak tumoricidal effects. Therefore, the observed leukocyte infiltration in melanoma might be at least in part an epiphenomenon of neoplastic self-stimulation rather than a full-fledged innate anti-tumor immune response.     

Chemokines in tumor angiogenesis and metastasis

Chemokines are a large group of low molecular weight cytokines that are known to selectively attract and activate different cell types. Although the primary function of chemokines is well recognized as leukocyte attractants, recent evidences indicate that they also play a role in number of tumor-related processes, such as growth, angiogenesis and metastasis. Chemokines activate cells through cell surface seven trans-membranes, G-protein-coupled receptors (GPCR). The role played by chemokines and their receptors in tumor pathophysiology is complex as some chemokines favor tumor growth and metastasis, while others may enhance anti-tumor immunity. These diverse functions of chemokines establish them as key mediators between the tumor cells and their microenvironment and play critical role in tumor progression and metastasis. In this review, we present some of the recent advances in chemokine research with special emphasis on its role in tumor angiogenesis and metastasis.     

趋化因子CCL21的研究进展

趋化因子CCL21属于CC类趋化因子,主要表达于周围淋巴组织.研究表明,CCL21可以促使血管内皮细胞黏附流动的T细胞参与淋巴细胞归巢,能够很强地趋化T、B淋巴细胞、成熟树突状细胞(DC)及NK细胞,参与T细胞免疫应答.CCL21可以募集活化效应细胞,使其肿瘤周围聚集,在肿瘤治疗方面具有较大潜力.CCL21的高表达也与许多免疫疾病的发生相关.     

Enhancement of anti-tumor immunity by tumor cells transfected with the secondary lymphoid tissue chemokine EBI-1-ligand chemokine and stromal cell-derived factor-1alpha chemokine genes

Several new lymphocyte-specific chemokines, which attract naive and memory T cells, B cells, dendritic cells and natural killer cells, have been isolated. We have found evidence of the anti-tumor effects of 3 major lymphocyte-specific chemokines, secondary lymphoid tissue chemokine (SLC), EBI-1-ligand chemokine (ELC) and stromal cell-derived factor (SDF)-1alpha, in murine models (Meth A fibrosarcoma and HM-1 ovarian tumor). In both naive and immunized mice, tumors expressing SLC, ELC or SDF-1alpha showed delayed progression compared with control tumors. In mice immunized with tumor cells expressing 1 of these 3 chemokine genes, challenge with parental tumor cells resulted in slightly slower progression than in control mice, while in mice immunized with tumor cells transfected to co-express IL-2 or granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as these chemokines, all tumors regressed. Furthermore, spleen cells from mice immunized with these "double-transfected" tumor cells exhibited higher proliferative responses and greater cytotoxic activity against parental tumor cells. These anti-tumor effects were associated with profound alterations in the leukocyte populations within the tumors and regional lymph nodes, and this was due to activation of type I T cell-dependent responses that produced high levels of IFN-gamma. These findings show that SLC, ELC and SDF-1alpha enhance anti-tumor immunity both systemically and locally and that these chemokines may be clinically useful, especially when combined with IL-2 and GM-CSF.     

胆固醇代谢调控CD8+T细胞抗肿瘤作用的研究进展

CD8+T细胞又名细胞毒性T淋巴细胞（cytotoxic T lymphocyte,CTL）,具有直接杀死病原体感染细胞和癌细胞的作用。然而,CD8+T细胞常常丧失其效应功能,继而限制肿瘤微环境中的抗肿瘤免疫,因此,如何重新激活CD8+T细胞的抗肿瘤效力是目前需要解决的问题。最近研究发现,胆固醇代谢在肿瘤中发挥重要作用,胆固醇有助于T细胞受体的积聚和免疫突触的形成,T细胞的效应功能也会被其代谢所影响,肿瘤细胞可利用胆固醇代谢诱导T细胞耗竭和逃避T细胞免疫监视。目前针对胆固醇代谢与CD8+T细胞免疫效应新分子和新策略的筛选已成为肿瘤研究领域的热点,本文综合关于胆固醇与CD8+T细胞方面的重要研究,阐述胆固醇代谢及在CD8+T细胞抗肿瘤活性中的作用机制,为后续研究提供参考。     

CCL2 (monocyte chemoattractant protein-1) and cancer

Genetic analyses of cancer in humans indicate that chemokines and their receptors are unlikely to play direct roles in pathogenesis. However, these molecules have pleiotropic effects that impact on cancer pathobiology in animal models, and there is evidence that they may do the same in humans. Given their protean properties, chemokines could have tumor-promoting, tumor-suppressing activities, or either depending on context. An example is found in CCL2, a chemokine that attracts and activates mononuclear cells. In some settings, it stimulates host anti-tumor activities. However, tumor cells themselves secrete CCL2 suggesting that it has growth promoting effects. These have been documented in animal models and clinical epidemiological studies. If CCL2's protumorigenic activities can be validated, then CCL2 and its receptor CCR2 may be therapeutic targets in cancer.     

德氮吡格及其衍生物抗肿瘤研究进展

脂代谢在肿瘤发展和侵袭中有至关重要的作用，已成为肿瘤细胞最重要的代谢标志之一。过氧化物酶体增殖物激活受体 γ（peroxisome proliferator activated receptor γ，PPARγ）配体或激动剂对多种肿瘤均有良好的抗肿瘤作用。德氮吡格是自主研发的创新结构抗肿瘤药，体内外实验表明其抗肿瘤作用显著，呈现非细胞毒性，已证实PPARγ是其作用靶点。本文对德氮吡格及其衍生物的抗肿瘤作用及其机制进行综述。     

Chemerin在代谢综合征相关肿瘤治疗中的作用及机制

代谢综合征是一组以胰岛素抵抗为核心，多种代谢异常簇集发生在同一个体的临床状态，与许多恶性肿瘤的发生有关。脂肪组织可分泌大量脂肪因子，参与代谢综合征及其相关肿瘤的发生发展。Chemerin是近年新确认的脂肪因子，具有促进脂肪分化和炎症反应、影响胰岛素抵抗及调节脂代谢等作用，参与代谢综合征极其相关疾病的进程。此外，作为一种趋化因子，Chemerin可介导肿瘤微环境中多种免疫细胞募集，发挥抗肿瘤作用。本文将针对Chemerin在代谢综合征相关肿瘤治疗中的作用及机制进行综述。