调节性T细胞在乙型肝炎中免疫作用的研究现状

乙型肝炎是由乙型肝炎病毒(hepatitis B virus,HBV)引起的流行性、进展性传染病。目前全球有1/3人口为HBV感染者,约3.6亿人为无症状HBV携带者,每年因感染HBV死亡的人数约50～120万,     

调节性T细胞在胃癌周围组织及癌组织中的表达意义

目的探讨调节性T细胞在胃癌周围组织及癌组织中的表达意义。方法选取30例胃癌患者及30例健康体检者(对照组)为研究对象,胃癌患者均经手术病理及胃镜检查确诊。采用流式细胞仪检测两组外周血组织中的CD4+CD25+Foxp3+的表达。同时留取胃癌患者癌组织和癌旁组织,对Foxp3细胞的表达情况进行免疫组化检查,并将其与胃癌的临床分期、分化程度、肿瘤部位等相关性进行分析。结果胃癌患者外周血中CD4+CD25+Foxp3+的百分比高于对照组,差异有统计学意义(P<0.05)。胃癌组织中的Foxp3+T细胞表达水平高于癌旁组织,差异有统计学意义(P<0.05)。胃癌组织中的Foxp3+T细胞表达水平与临床分期、淋巴结转移、分化程度因素相关,差异有统计学意义(P<0.05)。结论胃癌患者外周血中的CD4+CD25+Foxp3+及胃癌组织中的Foxp3+显著增加,在胃癌的预测和诊断中有一定的临床检测意义。     

STAT3信号通路对胃癌患者外周血调节性T细胞的作用机制分析

目的 分析信号转导与转录因子3(STAT3)信号通路对胃癌患者外周血调节性T细胞的作用机制.方法 回顾性纳入2017年11月至2020年11月于滨州医学院烟台附属医院进行治疗的80例胃癌患者为观察组,并纳入同期行健康检查的80例健康志愿者为对照组.比较2组外周血调节性T细胞变化及对T效应细胞(Tresp细胞)功能的影响...     

肾癌组织FoxP3细胞局部浸润与预后的关系

目的探讨肾癌组织局部浸润Fox P3+细胞的水平及其与临床病理及预后的关系。方法采用免疫组织化学染色检测2004年7月至2014年9月在中山大学附属第三医院岭南医院行手术治疗的62例肾癌患者的肿瘤内部、边缘及正常组织局部浸润Fox P3+细胞的水平,统计临床病理资料及随访记录,并分析肾癌组织局部浸润Fox P3+细胞的水平及其与临床病理及预后的关系。结果肾癌肿瘤内部及边缘浸润的Fox P3+细胞数目平均为(10.6±7.0)个/高倍镜视野(HP)、(14.5±9.5)个/HP,与正常组织比较差异均有统计学意义(P<0.05)。肿瘤内部及肿瘤边缘的浸润Fox P3+细胞数目与肿瘤大小(r=-0.084,P=0.514;r=-0.062,P=0.634)、肿瘤分期(r=-0.155,P=0.228;r=-0.031,P=0.814)、核分级(r=-0.095,P=0.480;r=-0.057,P=0.672)及病理类型(r=-0.079,P=0.540;r=-0.108,P=0.405)均不相关,并且其不同水平下总生存期也无差异(P=0.138;P=0.068)。结论肾癌组织局部浸润的Fox P3+细胞较正常组织明显升高,但与肾癌的预后及功能的关系尚有待进一步研究。     

腹腔热灌注化疗对晚期胃癌患者外周血和腹水调节性T细胞的影响及意义

目的探讨腹腔循环热灌注化疗对晚期胃癌患者外周血和腹水CD4~+CD25~+调节性T细胞(Treg细胞)的影响和意义。方法 48例胃癌合并腹水患者,采用替吉奥(S-1)联合顺铂腹腔循环热灌注化疗方案治疗2周期后参照世界卫生组织(WHO)标准进行疗效评价。采用流式细胞术检测有效组和无效组化疗前后外周血及腹水中Treg细胞比例变化。结果 48例患者中,完全缓解(CR)2例,部分缓解(PR)30例,无效(NC)11例,进展(PD)5例,腹水有效控制率(CR+PR)为66.67%(32/48)。腹水的Treg细胞比例均高于外周血(P0.05)。有效组化疗后外周血和腹水中Treg细胞比例均较化疗前下降(P0.05);无效组化疗前后Treg细胞比例变化不明显(P0.05)。化疗前两组间外周血及腹水中Treg细胞比例比较,差异无统计学意义(P0.05);化疗后两组间外周血及腹水中Treg细胞比例比较,差异有统计学意义(P0.05)。结论 S-1联合腹腔热灌注化疗可有效治疗胃癌合并腹水,可能主要通过杀伤肿瘤的方式,间接解除Treg细胞的免疫抑制作用。     

胃癌外周血调节性T细胞表达与预后的关系

目的：探讨胃癌患者外周血中CD4^＋CD25^＋、CD4^＋FOXP3^＋、CD4^＋CD25^＋FOXP3^＋调节性T细胞的表达状态与临床病理特征及预后关系。方法：采用流式细胞术检测35例胃癌患者及17例健康对照者外周血中CD4^＋CD25^＋、CD4^＋FOXP3^＋、CD4^＋CD25^＋FOXP3^＋调节性T细胞占CD4^＋T细胞的比率及细胞数目;收集胃癌患者临床病理资料并进行术后随访,分析调节性T细胞表达状态与临床病理特征及无瘤生存率之间的关系。结果：胃癌患者外周血中CD4^＋CD25^＋、CD4^＋FOXP3^＋及CD4^＋CD25^＋FOXP3^＋调节性T细胞占CD4^＋T细胞比率与健康对照者间有显著差异（P〈0.01）,CD4^＋FOXP3^＋及CD4^＋CD25^＋FOXP3^＋调节性T细胞数目与健康对照间差异有统计意义（P〈0.05）。CD4^＋CD25^＋FOXP3^＋调节性T细胞占CD4^＋T细胞的比率[（2.57±1.50）%]高于对照组[（0.68±0.67）%],并与TNM分期及肿瘤大小有明显相关（P〈0.01）。CD4^＋FOXP3^＋、CD4^＋CD25^＋FOXP3^＋调节性T细胞占CD4^＋T细胞的比率与无瘤生存率相关,有显著差异（P〈0.01）,CD4^＋FOXP3^＋及CD4^＋CD25^＋FOXP3^＋调节性T细胞数目与无瘤生存率相关,差异有统计学意义（P〈0.05）。结论：CD4^＋FOXP3^＋及CD4^＋CD25^＋FOXP3^＋调节性T细胞可能在胃癌免疫耐受中发挥重要作用,检测其比率及数目对于判断胃癌的病期及预后有一定价值。     

多发性骨髓瘤调节性T细胞研究进展

多发性骨髓瘤(MM)是浆细胞恶性增殖性疾病,免疫异常在其发病机制中起重要作用.调节性T细胞(Treg)在维持人体正常免疫中扮演重要角色.现将介绍Treg的生物学特性及其在MM患者中的数量、功能变化及可能的作用途径.     

子宫内膜异位症患者外周血中CD4+CD25+FoxP3+调节性T细胞的表达及意义

目的：探讨子宫内膜异位症患者外周血 CD4+CD25+FoxP3+调节性 T 细胞（CD4+CD25+FoxP3+ Treg）的表达及意义。方法选择2012年10月至2013年9月云南省第一人民医院收治的65例子宫内膜异位症患者、30例子宫肌瘤患者及20例健康体检者,应用流式细胞仪检测3组的外周血 CD4+CD25+FoxP3+ Treg 百分率,并进行比较。结果子宫内膜异位症组患者外周血中的 CD4+CD25+FoxP3+ Treg 占 CD4+ T 淋巴细胞的比例显著高于子宫肌瘤组患者及健康体检者,组间差异有统计学意义（P<0.001）;而子宫肌瘤患者与健康体检者外周血中的 CD4+CD25+FoxP3+ Treg 占 CD4+ T 淋巴细胞的比例差异无统计学意义（P>0.05）。结论 CD4+CD25+FoxP3+ Treg 在子宫内膜异位症患者外周血中的表达显著增加,明显高于非子宫内膜异位症患者,提示机体免疫异常与子宫内膜异位症的发生存在密切关系。     

乳腺癌患者外周血T淋巴细胞及调节性T细胞的检测意义

目的 探讨乳腺癌患者外周血中T淋巴细胞亚群及调节性T细胞的变化和临床意义.方法 采用流式细胞技术检测30例乳腺癌患者外周血中T淋巴细胞亚群及调节性T细胞的变化,并与健康对照组进行比较.结果 乳腺癌患者外周血CD4+CD25+及CD4+CD25+high调节性T细胞占CD3+CD4+T细胞的比率为(15.52±1.54)%及(3.49±0.54)%,高于健康对照组(6.11±0.72)%及(1.42±0.61)%,差异有统计学意义(P<0.05);乳腺癌患者CD3+T淋巴细胞比率为(50.98±6.79)%、CD4+Th细胞比率为(28.37±7.58)%和Th/Ts比值为(1.05±0.38),显著低于健康对照组(67.55±5.98)%、(40.12±5.27)%和(1.59±0.65),差异有统计学意义(均P<0.05),而CD8+Ts细胞比率为(30.05±7.79)%,与健康对照组(29.97±7.14)%比较,差异无统计学意义(P>0.05).结论 乳腺癌患者外周血调节性T细胞水平升高,T淋巴细胞及Th细胞降低可能是乳腺癌患者细胞免疫功能受损的重要原因之一.     

调节性T细胞的新标记CD4+CD25+CD127low/-在类风湿性关节炎中的应用

目的 选择用膜表面标志CD4+CD25+CD127low/-作为检测调节性T(Treg)细胞的指标,探讨其在类风湿性关节炎(RA)中的可能临床应用价值.方法 用流式细胞术检测正常人及RA患者外周血CD4+CD25high、CD4+ CD25+ FoxP3+ 和CD4+CD25+CD127low/- T细胞占CD4+T细胞的比例,分析CD4+CD25+CD127low/-与CD4+ CD25+ FoxP3+ 2群细胞比例之间的相关性.结果 正常人及RA患者外周血CD4+CD25+CD127low/-T细胞比例与CD4+ CD25+ FoxP3+T细胞比例之间呈显著正相关(r=0.694、0.768,P均＜0.01).RA患者外周血CD4+CD25high、CD4+ CD25+ FoxP3+及CD4+CD25+CD127low/-T细胞比例均显著低于正常人(P均＜0.01).结论 膜表面标志CD4+CD25+CD127low/-可以用来鉴定Treg细胞,RA患者外周血CD4+CD25+CD127low/-T细胞的明显减少可能是RA的发病机制之一.     

调节性T细胞在胰腺癌免疫治疗中的作用机制与应用策略

免疫治疗在胰腺癌的临床试验中疗效欠佳,主要原因在于胰腺癌具有高度免疫抑制的肿瘤微环境（tumor microenvironment, TME）。调节性T细胞（regulatory T cells, Tregs）是一类控制自身免疫反应的T细胞亚群,也是免疫抑制性TME的主要组成成分之一。Tregs能调控机体免疫反应强度,抑制效应T细胞的功能和活性进而诱导免疫耐受,维持免疫应答稳态。在胰腺癌TME中,Tregs通过抑制机体免疫反应从而介导肿瘤细胞发生免疫逃逸,影响患者的疗效与预后。本综述总结Tregs在胰腺癌免疫微环境中的作用机制及在胰腺癌中的临床意义,以期为胰腺癌免疫治疗提供更多的新思路。     

Induced regulatory T cells in inhibitory microenvironments created by cancer

Introduction: Regulatory T cells (Tregs) accumulating in the peripheral circulation and tumor sites of patients contribute to tumor escape from the host immune system. Tregs encompass subsets of immune cells with distinct phenotypic and functional properties. Whereas natural (n) or thymic-derived (t) Tregs regulate responses to self-antigens, inducible (i) or peripheral (p) Tregs generated and expanded in regulatory microenvironments control immune responses to a broad variety of antigens.

Areas covered: Tregs accumulating in the tumor microenvironment (TME) are contextually regulated. They acquire phenotypic and functional attributes imposed by the inhibitory molecular pathways operating in situ. Several molecular pathways active in human cancer are reviewed. The pathways may differ from one tumor to another, and environmentally induced Tregs may be functionally distinct. Potential therapeutic strategies for selective silencing of iTregs are considered in the light of the newly acquired understanding of their phenotypic and functional diversity.

Expert opinion: Human Tregs accumulating in cancer comprise ‘bad’ subsets, which inhibit antitumor immunity, and ‘good’ anti-inflammatory subsets, which maintain tolerance to self and benefit the host. Future therapeutic strategies targeting Tregs will need to discriminate between these Treg subsets and will need to consider reprogramming strategies instead of Treg elimination. Re-establishment of effective antitumor immune responses in cancer patients without disturbing a normal homeostatic T-cell balance will greatly benefit from insights into inhibitory pathways engaged by human tumors.     

Induced and natural regulatory T cells in human cancer

Introduction: Evidence suggests that FOXP3⁺CD25^highCD4⁺ regulatory T cells (Treg) which accumulate in cancer may have beneficial or unfavorable effects on prognosis. The presence in tumor-associated inflammatory infiltrates of two subsets of Treg with distinct phenotypic and functional profiles might explain these conflicting observations.

Areas covered: Human inducible (i) Treg arising by tumor-driven conversion of conventional CD4⁺ T cells are highly suppressive, therapy-resistant Treg which down-regulate anti-tumor immune responses, promoting tumor growth. Natural (n) Treg, normally responsible for maintaining peripheral tolerance, control cancer-associated inflammation, which favors tumor progression. This division of labor between nTreg and iTreg is not absolute, and overlap may be common. Nevertheless, iTreg play a critical and major role in cancer and cancer therapy. The tumor microenvironment determines the type, frequency and suppression levels of accumulating Treg.

Expert opinion: In cancer, a selective removal or silencing of iTreg and not of nTreg should be a therapeutic goal. However, the implementation of this challenging strategy requires further studies of cellular and molecular crosstalk among immune cells in the tumor microenvironment.     

CD4+CD25+Foxp3+调节性T细胞在CIK细胞诱导中的表达及其功能

目的探讨肿瘤患者自体细胞因子诱导的杀伤细胞(CIK)诱导过程中CD4~+CD25~+Foxp3~+调节性T细胞的变化及其功能。方法应用血细胞分离机采集22例肿瘤患者外周血单个核细胞(PBMC),诱导培养CIK细胞,用流式细胞仪动态监测其CD4~+CD25~+Foxp3~+表型,并分析Tregs细胞负性调控分子转化生长因子-β1(TGF-β1)、细胞毒性T淋巴细胞相关抗原4(CTLA-4)和IL-10的表达水平,采用细胞增殖抑制试验测定Tregs细胞免疫学功能。结果诱导的CIK细胞中存在CD4~+CD25~+Foxp3~+Tregs,其表达量分别为第1天(0.30±0.15)%、第3天(4.48±1.72)%、第5天(3.83±2.12)%、第9天(2.37±1.17)%、第11天(1.65±0.99)%、第14天(1.04±0.76)%。诱导第14天时的Tregs细胞免疫调控负性分子TGF-β1的表达水平为(97.2±2.1)%、CTLA-4为(96.2±3.5)%、IL-10为(4.2±2.3)%。细胞增殖抑制试验中空白对照组、条件对照组以及实验组的增殖细胞表达量分别为(8.55±2.38)%、(42.66±7.32)%、(57.04±7.49)%。结论 CD4~+CD25~+Foxp3~+Tregs细胞可作为潜在的CIK细胞质量评价指标。     

Phenotypic alterations,clinical impact and therapeutic potential of regulatory T cells in cancer

Introduction: Regulatory T cells (Tregs) have been characterised in different cancers. They accumulate in peripheral blood and tumour microenvironments where they suppress tumour-specific immune responses, enabling tumours to develop without challenge. This tumour immune evasion represents a major obstacle to successful cancer therapies. Whilst Tregs are generally divided into thymic-derived and peripherally induced, Tregs exhibit a wide spectrum of phenotypes and functional capacity dependent on microenvironment. This phenotypic diversity is also reflected in tumour-infiltrating Treg (TI Treg) populations, which may explain the variable impact of Treg accumulation on prognosis in different cancers. Identifying TI Treg subsets is critical to understand TI Treg biology and for developing effective immunotherapies.

Areas covered: This review discusses current and potential markers, and the modulation of these markers in cancer. In addition, we systematically review the clinical impact of Tregs in cancer and their potential as a therapeutic target, with a focus on TI Tregs.

Expert opinion: TI Tregs represent dynamic and diverse subsets that are key in promoting tumour progression through their suppressive activities. Targeting specific TI Treg subpopulations and functional TI Treg markers represents a feasible therapeutic strategy that might allow reestablishment of antitumour immune responses without affecting physiological immune regulation.     

T regulatory cells in cancer: recent advances and therapeutic potential

Importance of the field: The active suppression of immune responses against tumor is a major barrier to the likely success of cancer immunotherapy. There is now compelling evidence implicating T regulatory cells (Tregs) as being key players driving immune suppression. Elevated frequencies of Tregs within the peripheral circulation and tumor microenvironment of cancer patients correlate with poor prognosis and reduced survival. Understanding the mechanism of Treg elevation is critical for the development of new approaches aiming to modulate the frequency and function of Tregs to enhance the efficacy of cancer immune-based therapies.

Areas covered in this review: This review focuses on current knowledge concerning Tregs in cancer and discusses putative mechanisms which underlie the expansion of Tregs in cancer patients. Additionally, we review current strategies to deplete/suppress Treg activity, the limitations of these strategies and future perspective for improving their efficacy.

What the reader will gain: An insight of the current aspects concerning Treg subsets in cancer and an overview of recent advances in the identification of Treg-specific markers, in addition to the potential strategies to target Tregs for enhancing antitumor immunity.

Take home message: Mechanisms by which Treg functions modulate the immune response to tumors are becoming further understood. However, specific markers to tumor-specific/induced Tregs are yet to be clearly identified, which is a major limitation in optimizing strategies to specifically target Tregs in cancer. Despite this, strategies aimed at modulating Tregs in patients are providing some early encouraging results supporting the overall concept and indicating that further studies are clearly warranted.     

非小细胞肺癌患者外周血调节性T细胞表达及意义

目的探讨CD4+CD25+,CD8+CD28-调节性T细胞及其亚群表型CD45RO在非小细胞肺癌(non-small cell lung cancer,NSCLC)患者外周血中表达及其与NSCLC临床病理及手术的关系。方法采用流式细胞仪检测40例NSCLC患者和20例对照外周血中CD4+CD25+,CD8+CD28-,CD8+CD28+T细胞亚群比率,并对其亚群表型CD45RO进行检测。结果 NSCLC组CD4+CD25+,CD4+CD25+CD45RO+,CD8+CD28-细胞亚群比率较对照组明显升高(P<0.05);CD8+CD28+细胞亚群比率较对照组明显降低(P<0.01);NSCLC组手术后CD4+CD25+细胞亚群比率较术前明显降低(P<0.01),CD8+CD28+细胞亚群比率较术前明显升高(P<0.01);外周血调节性T细胞水平与NSCLC临床病理无相关性(P>0.05)。结论 CD4+CD25+,CD8+CD28-和CD8+CD28+T细胞亚群比率的改变可能与肺癌免疫耐受和抗肿瘤能力下降有关;手术治疗可下调患者机体的肿瘤免疫耐受,改善患者抗肿瘤免疫功能。     

D-二聚体和肿瘤标记物在胃癌中的诊断价值

目的研究血清中凝血5项[凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)、D-二聚体(D-D)]与肿瘤标志物[癌胚抗原(CEA)、甲胎蛋白(AFP)、糖类抗原724(CA724)、糖类抗原199(CA199)、细胞角蛋白19片段(CYFRA21-1)以及神经元特异性烯醇化酶(NSE)]联合检测在胃癌诊断中的价值。方法选取2017年8月至2019年4月安徽医科大学第三附属医院肿瘤科收治的126例胃癌患者为A组,124例良性胃病患者为B组,同期134例健康体检者为C组。检测并比较3组受试者的凝血5项(PT、APTT、TT、FIB、D-D)与肿瘤标志物(CEA、AFP、CA724、CA199、CYFRA21-1)水平。结果A组中D-D、CEA、CA724、CYFRA21-1水平高于B组和C组,差异有统计学意义(P<0.05)。A组的AFP、CA199、NSE、PT、APTT、FIB、TT与B组和C组相比,差异均无统计学意义(P>0.05)。随着肿瘤分期的延长,胃癌患者血清中的D-D、CEA、CA724、CYFRA21-1表达水平均显著升高,进行联合检测可提高诊断的灵敏度和特异度。结论D-D、CEA、CA724、CYFRA21-1联合检测可提高诊断的灵敏度和特异度,对胃癌的诊断具有一定的价值。