肿瘤微环境在肿瘤免疫治疗中的研究进展

肿瘤的免疫治疗是继放疗、化疗和手术治疗之后的第4种有效的治疗方法。但大量的临床研究证实,其治疗效果并不好,这与肿瘤微环境有着密不可分的关系。本文就效应T细胞、肿瘤细胞及周围炎症因子对肿瘤免疫治疗的研究现状做一综述。     

巨噬细胞在肿瘤免疫治疗中的研究进展

巨噬细胞在肿瘤发生发展的作用复杂,肿瘤相关巨噬细胞(Tumor-associated macrophage,TAM)在肿瘤的生长、血管形成,侵袭转移等方面具有促进作用;肿瘤组织形成的免疫抑制性微环境会对TAM 进行“再教育冶,影响肿瘤微环境中TAM 的表型和功能。通过多种途径对巨噬细胞的功能和表型进行干预和改造,可增强巨噬细胞在肿瘤微环境中的识别、吞噬和抗原提呈能力,促进巨噬细胞对肿瘤的杀伤。     

应用IL-12进行肿瘤免疫治疗的新进展

ＩＬ１２ 是一种重要的抗肿瘤细胞因子,它主要有以下作用：激发ＮＫ／ＬＡＫ 细胞及Ｔ细胞的增殖,分化及向肿瘤部位趋化;诱导ＩＦＮγ的产生;促进巨噬细胞释放ＮＯ;抑制肿瘤血管形成等。应用ＩＬ１２ 进行抗肿瘤治疗可通过以下途径：直接给予ＩＬ１２ 蛋白;将克隆入ＩＬ１２ 基因的细胞注射至肿瘤生长部位;用含ＩＬ１２ 基因的病毒感染肿瘤细胞;直接将含ＩＬ１２ 基因的质粒注入体内。另外它尚可作为免疫佐剂增强ＡＰＣ细胞提呈肿瘤特异性抗原的能力。     

纳米材料在肿瘤免疫治疗中的应用

肿瘤免疫治疗由于生物效应高、毒副作用小、可有效抑制肿瘤转移及复发等优势,已成为临床恶性肿瘤的主要治疗方式之一,然而复杂的肿瘤微环境及肿瘤的异质性限制了其治疗效果。近年来,纳米材料因具有载药量大、肿瘤靶向性强、易修饰等优点,能有效克服传统免疫疗法的弊端,被广泛应用于肿瘤免疫治疗。本文综述了近年来基于纳米材料的肿瘤免疫治疗研究进展,为探索新的肿瘤免疫治疗策略提供理论基础。     

抗独特型抗体在肿瘤免疫治疗中的研究进展

应用抗独特型抗体（抗-Id）疫苗激活抗肿瘤免疫是治疗肿瘤的有效途径之一。大量动物研究证明，抗-Id在预防肿瘤生长和抗肿瘤治疗方面是非常有效的。许多抗独特型抗体模拟特异性人肿瘤相关抗原（TAAs），在临床应用获得令人鼓舞的效果。抗独特型抗体免疫治疗最大的挑战是确定替代TAAs功能并刺激机体产生体液、细胞免疫的最佳抗独特型抗体。本文从实验室研究和临床研究方面综述了近年来抗独特型抗体在肿瘤免疫治疗研究中的进展。     

IL-21及其在自身免疫病中的研究进展

白介素-21(IL-21)是近年来被发现和关注的一个四螺旋束的细胞因子,主要由活化的CD4~+Th细胞和NKT细胞分泌,与IL-2、IL-4和IL-15具有高度同源性。它的受体属于Ⅰ型细胞因子受体,由α链和γc链组成,广泛分布于T细胞、B细胞、自然杀伤细胞、树突状细胞、巨噬细胞和角质化细胞等细胞表面,在固有免疫和适应性免疫中发挥重要作用。IL-21具有多效性,在类风湿性关节炎、系统性红斑狼疮、炎症性肠病等一些自身免疫病的发病机制中起着重要的作用。本文就IL-21及其与自身免疫病的关系作一综述。     

肿瘤免疫治疗研究进展

肿瘤细胞可通过一系列免疫逃避机制躲避机体免疫攻击,从而在体内肆意繁殖,侵犯机体正常组织.近年来,随着肿瘤学、免疫学以及分子生物学等相关学科的迅速发展和交叉渗透,免疫学治疗方法因其能有效杀伤肿瘤细胞且对机体副作用较小,越来越受到人们的重视,其疗效评价也因免疫治疗的特殊性而有别于一般的实体瘤治疗.就肿瘤免疫治疗的最新进展作一综述.     

树突状细胞疫苗在妇科肿瘤免疫治疗中的研究进展

树突状细胞(DC)具有摄取、加工、处理和呈递抗原以及激活初始T淋巴细胞的功能,是体内功能最强的专职抗原递呈细胞,也是免疫应答的关键细胞.近年来研究发现,体外经肿瘤抗原刺激的DC回输到病人体内,能诱导机体产生细胞毒性T淋巴细胞,从而发挥特异性肿瘤杀伤作用.根据这一发现研制的DC疫苗目前在妇科肿瘤免疫治疗中已取得重要进展,...     

T细胞受体与肿瘤免疫治疗

肿瘤免疫治疗已明确有大量Ｔ淋巴细胞浸润到肿瘤组织，在一定肿瘤中Ｔ细胞受体（ＴＣＲ）Ｖ区受体库（ｒｅｃｅｐｔｏｉｒｅ）明显表达与识别肿瘤相关抗原（Ｔｕｍｏｒ－ａｓｓｏｃｉａｔｅｄａｎｔｉｇｅｎＴＡＡ）有关，形成的ＴＣＲ－ＭＨＣ－肽三元复合物，在共刺激因子（Ｃｏｓｔｉｍｕｌａｔｉｎｇｆａｃｔｏｒ）参与下发挥细胞毒效应，本文进一步评估了用Ｔ细胞进行免疫治疗的前景。     

细胞工程技术在肿瘤免疫治疗药物中的现状和应用

细胞工程是生物工程的一个重要组成部分,近年取得了极大发展,已被广泛应用于医药、畜牧业和环境保护等许多领域,取得了较好的社会效益和经济效益. 做为一门应用科学和工程技术,细胞工程形成的历史还很短,因此定义还不十分完善.     

IL-21 and IL-21 receptor in the immunopathogenesis of multiple sclerosis

Cytokines are considered important factors in the modulation of various immune responses. Among them, interleukin (IL)-21 is one of the major immune modulators, adjusting various immune responses by affecting various immune cells. It has been suggested that IL-21 may enhance autoimmunity through different mechanisms, such as development and activation of helper T (T_H)-17 and follicular helper T (T_FH) cells, activation of natural killer (NK) cells, enhancing B-cell differentiation and antibody secretion and suppression of regulatory T (T_reg) cells. Moreover, IL-21 has also been suggested to be an inducer of autoimmunity when following treatment of MS patients with some therapeutics such as alemtuzumab. This review will seek to clarify the precise role of IL-21/IL-21R in the pathogenesis of MS and, in its animal model, experimental autoimmune encephalomyelitis (EAE).     

IL-21 and IL-21 receptor

Interleukin (IL)-21 is a new member of the type I cytokine superfamily. Although it is most homologous to IL-15, it has a unique receptor chain, IL-21R, that pairs with the γ-common cytokine receptor chain. The first experiments examining the biology of the IL-21 pathway reveal that it is a cytokine with effects on natural killer (NK) cells, T cells, and B cells. Mice deficient in the IL-21 R have also been made, and are being examined for the effects of the IL-21/IL-21R pathway in vivo. Here we summarize our current knowledge of this new cytokine pathway, and its role in innate and adaptive immunity.     

IL-21 synergizes with IL-7 to augment expansion and anti-tumor function of cytotoxic T cells

IL-21, a recently identified member of the common gamma-chain (gammac) receptor cytokine family, has been shown to be an important regulator of both innate and adaptive immune responses. In this study, we investigated whether IL-21 could synergize with another gammac cytokine, IL-7, to induce enhanced proliferation and effector function of tumor antigen-specific CD8(+) T cells. Our results showed that IL-21 could significantly augment the IL-7-induced expansion of cytotoxic T cells, possibly by preventing the cytokine-induced down-regulation of the IL-7Ralpha (CD127) on antigen-stimulated T cells. IL-21 also greatly enhanced the production of T(h)1 and inflammatory cytokines by activated T cells, including IFN-gamma, IL-2, tumor necrosis factor-alpha, granulocyte macrophage colony-stimulating factor, IL-1beta and IL-6. Finally, the addition of IL-21 to IL-7-cultured CTLs resulted in a considerably higher level of cytolytic activity, as measured by specific killing of tumor cells or antigen-pulsed target cells. These results suggest that IL-21 may play a cooperative role with IL-7 in modulating primary CD8(+) T-cell responses and may have important implications for immunotherapy of cancer.     

IL-21在Th17细胞炎症反应中的作用

Th17细胞是新近发现的T淋巴细胞亚群.作为不同于Th1、Th2的细胞亚群,已经被证实在自身免疫病、感染、炎症等疾病中发挥重要作用.IL-21作为Th17细胞的自分泌调节因子,在Th17细胞功能的维持、抑制Th1、调节性T细胞(Treg)分化等方面发挥关键作用.Th17细胞能够自分泌产生IL-21,从而促进自身分化过程...     

An overview of IL-7 biology and its use in immunotherapy

Interleukin (IL)-7 is required for T-cell development as well as for the survival and homeostasis of mature T-cells. In the thymus, the double negative (DN) CD4^? CD8^? thymocyte progenitor transition into double positive CD4⁺ CD8⁺ cells requires Notch and IL-7 signaling. Importantly, IL-7 seems to have a dose effect on T-cell development and, at high doses, DN progression is blocked. Naïve T-cells in the thymus, and after their exit to the periphery, are dependent on IL-7 and TCR signaling for survival. Upon antigen exposure, they proliferate and differentiate into memory T-cells. Because IL-7 intervenes at all stages of T-cell development and maintenance, it has been introduced recently into clinical trials as an immunotherapeutic agent for cancer patients (of particular note, those who had undergone T-cell depleting therapy) in an attempt to increase their population sizes of CD4⁺ and CD8⁺ cells overall, and specifically of CD8⁺ (CD45RA⁺CCR7⁺ and/or CD27⁺), CD4⁺ (CD45RA⁺CD31⁺), and CD4⁺ central memory T-cells (CD45RA^?CCR7⁺). Interestingly, IL-7 in humans induced a preferential expansion of naïve T-cells, resulting in a broader T-cell repertoire than before the treatment; this effect was independent of age. This suggests that IL-7 therapy could enhance immune responses in patients with limited naïve T-cell numbers as in aged patients or after disease-induced or iatrogenic T-cell depletion. This overview highlights the role of IL-7 on T-cells in mice and humans.     

肿瘤过继性细胞免疫治疗进展

过继性细胞免疫治疗(ACI)是肿瘤治疗的重要手段,通过回输体外扩增及激活的肿瘤特异性免疫细胞,达到控制肿瘤的目的.虽然ACI在恶性黑色素瘤的治疗中取得了可喜的疗效,但患者完全缓解率仍不足10％,而且ACI对其他肿瘤的临床疗效欠佳.近年来研究表明,改善细胞培养方法、优化成分组成、增强细胞本身功能以及联合其他治疗等是进一步提高肿瘤细胞免疫治疗的关键.     

Challenges and developing solutions for increasing the benefits of IL-2 treatment in tumor therapy

Interleukin-2 (IL-2) is a cytokine with pleiotropic effects on the immune system. Systemic IL-2 treatment has produced durable responses in melanoma and renal cancer patients, but unfortunately this is effective only in a fraction of patients. Moreover, IL-2 treatment also engenders serious side effects, which limit its clinical utility. It is now appreciated that IL-2 not only stimulates NK and effector T cells but also has a critical role in the generation and maintenance of regulatory T cells, which act to dampen immune responses. Thus, successful immunotherapy of cancers using IL-2 has to address two fundamentally important issues: (1) how to limit side effects yet be active where it is needed, and (2) how to preferentially activate effector T cells while limiting the stimulation of Tregs. Strategies are now being developed to address these critical obstacles that may lead to a renaissance of IL-2 therapy.     

非小细胞肺癌患者血清IL-17和IL-21水平变化及临床意义

目的 测定非小细胞肺癌(NSCLC)患者术前术后血清中IL-17、IL-21水平变化,探讨IL-17、IL-21水平在NSCLC诊断及预后中的临床意义.方法 采用酶联免疫分析法测定54名NSCLC患者术前以及术后血清IL-17、IL-21水平,随机选择30名健康志愿者作为正常对照组,检测其血清IL-17、IL-21水平并与之进行对比.结果 与正常对照组比较,NSCLC患者术前血清IL-17、IL-21水平差异具有统计学意义(P<0.01),术后差异无统计学意义(P>0.05).NSCLC患者术后与术前比较,血清IL-17水平明显降低(P<0.05),血清IL-21水平明显升高(P<0.05).晚期NSCLC患者血清IL-17水平高于早期NSCLC患者(P<0.05),而IL-21水平则低于早期NSCLC患者(P<0.05).结论 NSCLC患者血清中IL-17、IL-21水平变化与手术、NSCLC病程相关,监测IL-17、IL-21水平对NSCLC的治疗和预后有一定的指导意义.     

人外周血CD4~+ IL-21~+记忆T细胞的特征

目的:探讨人外周血中白细胞介素21(IL-21)的产生细胞及其特征。方法:分离人外周血单个核细胞(PBMC),分为不刺激或anti-CD3(OKT3)、OKT3+anti-CD28、PMA+ionomycin刺激四个组,流式细胞术(FCM)检测产生IL-21的细胞亚群。PMA+ionomycin刺激PBMC、纯化CD4+、CD4+CD45RA-、CD4+CD45RA+细胞、脐带血单个核细胞(CB-MC),FCM分析产生IL-21细胞的表型特征和IL-21与Th1、Th2、Th17和Th22细胞因子之间的关系。结果:与OKT3、OKT3+anti-CD28相比,PMA+ionomycin能诱导最高量的IL-21产生。产生IL-21的主要细胞为CD4+T细胞,少数CD8+T细胞。CD4+IL-21+T细胞表达CD45RO,不表达CD45RA,其中部分细胞表达CCR6、CCR7或CXCR5。CD4+CD45RA-细胞表达IL-21远高于CD4+CD45RA+细胞。进一步研究表明,PBMC产生IL-21,而CBMC不产生。此外,大约24%的CD4+IL-21+细胞表达IFN-γ,小于10%CD4+IL-21+细胞表达IL-4、IL-17或IL-22。结论:人PBMC在多克隆刺激的条件下,可以诱导IL-21的产生。产生IL-21的主要细胞亚群具有记忆CD4+T细胞的表型。其中一部分CD4+IL-21+T细胞的表型独立于Th1、Th2、Th17和Th22细胞亚群。