Th17 细胞及Treg细胞在非小细胞肺癌的免疫调节作用

CD4+T淋巴细胞是一类重要的免疫细胞,在不同细胞因子的诱导下,可分化为Th1 细胞、Th2 细胞、Th17 细胞和Treg 细胞等。Th17 细胞及Treg 细胞不仅具有多种生物免疫学效应,而且能够分泌不同的细胞因子,各种免疫细胞与细胞因子之间形成复杂网络,介导免疫反应,进行免疫调节,参与免疫相关性疾病的发生发展,如肿瘤、炎症、自身免疫性疾病等。近年来肺癌的发病率呈进行性升高,其中非小细胞肺癌（non-small cell lung cancer,NSCLC）占肺癌的比例最高。因此,本文将对Th17 细胞和Treg 细胞的分化及特点及在NSCLC中的免疫调节作用作一综述。     

肺癌射频消融术后CD4~+ T细胞亚群改变研究进展

CD4+T细胞包括Th1、Th2、Th17及Treg细胞,它们在肿瘤免疫中发挥重要作用。肺癌射频消融(radiofrequency ablation,RFA)术后可使Th1细胞升高、Th2细胞降低、Th1/Th2细胞免疫失衡得以纠正,Th17及Treg细胞降至正常水平。CD4+T细胞亚群的改变可作为肺癌RFA术后疗效评估和预后判断的指标。     

调节性T细胞诱导肿瘤免疫耐受的机制

调节性T细胞(Treg)是一类免疫抑制性T辅助(Th)细胞.研究表明,Treg可在肿瘤细胞分泌的趋化因子CCL22作用下大量募集于肿瘤周围,分泌或表达免疫抑制性的细胞因子和受体,形成以Th2型免疫为主的微环境,引导宿主免疫耐受.通过抗体等药物降低Treg数量和活性后可打破肿瘤免疫耐受,抑制肿瘤的发生和转移.     

非小细胞肺癌患者外周血Treg和Th17水平及意义

摘 要：［目的］ 探讨非小细胞肺癌(NSCLC)患者外周血中Treg和Th17细胞的变化及其意义。［方法］ 收集40例NSCLC患者和20名健康对照的外周血样本,采用流式细胞术检测外周血中Treg和Th17细胞占CD4+T细胞的比例,酶联免疫吸附实验法检测TGF-β和IL-17水平。［结果］ 肺癌患者外周血中Treg细胞和Th17细胞比例均显著性高于健康对照组(分别为6.65%±3.70% vs 4.06%±1.23%和1.20%±1.19% vs 0.44%±0.13%,P<0.05)。外周血Treg和Th17细胞表达与NSCLC患者分期等无相关性(P>0．05)。肺癌患者外周血TGF-β和IL-17水平明显高于对照组(分别为25.05±3.19 vs 15.96±3.65 和4.36±2.79 vs 2.01±1.83,P<0.05)。［结论］ NSCLC患者外周血中Treg和Th17细胞以及相关细胞因子均高表达,Treg细胞以及Th17细胞参与了肺癌的发生和发展。     

肺癌射频消融术后CD4＋ T细胞亚群改变研究进展

CD4＋T细胞包括Th1、Th2、Th17及Treg细胞,它们在肿瘤免疫中发挥重要作用。肺癌射频消融（radiofrequency ablation,RFA）术后可使Th1细胞升高、Th2细胞降低、Th1/Th2细胞免疫失衡得以纠正,Th17及Treg细胞降至正常水平。CD4＋T细胞亚群的改变可作为肺癌RFA术后疗效评估和预后判断的指标。     

急性白血病患者外周血Treg细胞与Th17细胞的相关性

目的:检测急性白血病患者外周血中Treg细胞与Th17细胞的比例以及相关细胞因子如IL-17、IL-6、TGF-β的变化,分析其相关性。方法:选取兰州大学第二医院血液科急性白血病初诊患者15例,另取15名健康志愿者为对照。流式细胞术检测外周血中CD3+CD4+TIL-17+辅助性T细胞(Th17细胞)、CD4+TCD25+Foxp3+调节性T细胞(Treg细胞)占CD4+T细胞的比例,ELISA法检测血清中细胞因子IL-17、TGF-β、IL-6的水平。结果:急性白血病患者外周血中Th17细胞占CD4+T细胞的(1.39±0.24)%,高于对照组的(0.26±0.11)%(P<0.05);急性白血病患者外周血Treg细胞占CD4+T细胞的(11.58±2.17)%,高于对照组的(2.47±0.72)%(P<0.05);且Treg细胞与Th17细胞呈正相关(γ=0.37)。急性白血病患者血清中TGF-β、IL-6、IL-17的水平分别为(26.06±2.43)、(14.66±2.47)、(18.63±2.38)pg/ml,高于对照组的(13.41±1.92)、(1.44±0.29)、(10.34±1.71)pg/ml(均P<0.05)。结论:急性白血病患者外周血中Treg、Th17细胞比例升高,且两者呈正相关;急性白血病患者血清中TGF-β、IL-6、IL-17水平升高,可能影响Treg与Th17细胞的平衡。     

调节性T细胞与肿瘤免疫

调节性T细胞( Treg)是一类有负调节作用的T细胞亚群,包括CD4+ Treg、CD8+ Treg、NKT Treg和DN Treg细胞等4大类,主要发挥抑制性免疫调节功能,是肿瘤免疫逃逸的重要因素.这些机制包括分泌多种免疫抑制性细胞因子、分泌颗粒酶和穿孔素杀伤效应细胞、竞争和抑制IL-2、通过T淋巴细胞毒性相关抗原(CTLA)-4影响Treg的分化和增殖等.以Treg及免疫抑制性分子作为靶点,清除Treg,控制Treg的数量和功能,增强机体对肿瘤的免疫应答,为肿瘤免疫治疗提供了新思路.     

晚期非小细胞肺癌合并慢性阻塞性肺疾病患者Th1/Th2及Th17/Treg与PD-1抑制剂治疗效果的关系

目的探讨晚期非小细胞肺癌(NSCLC)合并慢性阻塞性肺疾病(COPD)患者外周血辅助性T细胞1/辅助性T细胞2(Th1/Th2)、辅助性T细胞17/调节性T细胞(Th17/Treg)与程序性死亡受体1(PD-1)抑制剂疗效的关系。方法回顾性分析苏州大学附属苏州九院2021年4月至2022年9月收治的107例晚期NSCLC合并COPD患者的临床资料。患者均接受PD-1抑制剂治疗, 根据临床疗效将患者分为疾病控制组(82例)和疾病进展组(25例)。对比两组患者治疗前Th1/Th2、Th17/Treg及临床资料, 采用logistic回归分析患者PD-1抑制剂疗效的影响独立因素。结果治疗前疾病控制组Th1/Th2、Th17/Treg均高于疾病进展组(12.49±1.14比7.04±1.06, t=21.26, P<0.001;0.14±0.03比0.09±0.04, t=6.72, P<0.001)。与疾病控制组相比, 疾病进展组TNM分期Ⅳ期、存在淋巴结转移和脑转移患者比例均更高(均P<0.01)。多因素logistic回归分析结果显示, 治疗前Th1/Th2(OR=0....     

调节性T细胞与肿瘤免疫治疗的研究进展

调节性T细胞（Treg）在免疫系统中发挥负性调节作用,对维持机体免疫稳态起重要作用,其特征是CD4+CD25+叉头框蛋白P3(FOXP3)+。Treg在抗原识别、抗原呈递、免疫效应阶段都能发挥免疫抑制功能,通过多种细胞因子、激酶调控肿瘤微环境,在肿瘤免疫抑制和免疫逃逸中发挥重要作用。通过减少Treg数量或下调Treg功能可以起到抗肿瘤作用,针对这些靶点的药物单用或联合免疫检查点抑制剂治疗已取得较大进展。通过改变缺氧微环境,抑制血管生长也可以调控Treg功能。Treg可能与细胞毒性T淋巴细胞相关蛋白4(CTLA4)和程序性死亡受体1(PD-1)/程序性死亡受体配体1(PD-L1)单抗潜在的耐药和超进展有关,因此针对Treg的治疗可能有助于解决免疫检查点抑制剂在治疗中的一些问题。本文对Treg在肿瘤免疫中的作用机制予以综述,并阐述通过调控Treg发挥抗肿瘤作用的研究进展。     

调节性T细胞与肿瘤放疗

放射疗法（放疗）是当今治疗恶性肿瘤最常用的方法之一,中国肿瘤患者中约有70%接受放疗。放疗的免疫调节效应已经引起了极大的关注,越来越多的研究报道放疗和免疫治疗之间有很多协同之处。调节性Ｔ细胞(regulatory T cells,Treg)是一群具有免疫抑制性作用的细胞,与肿瘤关系密切,可通过细胞与细胞间接触、分泌抑制性的细胞因子以及干扰细胞代谢等方式参与到肿瘤的发病机制、进展以及肿瘤的治疗和预后等各个领域。该文以Treg的免疫学特性为出发点,系统的阐释肿瘤放疗与免疫分子的相互关系,旨在为肿瘤放疗联合Treg免疫治疗提供新的思路。     

Increased expression of immunosuppressive molecules on intratumoral and circulating regulatory T cells in non-small-cell lung cancer patients

The expression patterns of immunosuppressive molecules on regulatory T (Treg) cells have not been elucidated in non-small-cell lung cancer (NSCLC) patients. In this study, a total of 88 patients including 53 patients with NSCLC, 17 patients with lung non-malignant diseases, and 18 healthy volunteers were enrolled. Increased number of total CD4⁺CD25⁺FoxP3⁺ Treg cells and elevated expressions on the surface of several inhibitory molecules including CTLA-4, LAG-3 and PD-1 have been observed in the peripheral blood of NSCLC patients. We found that intratumoral Treg cells from NSCLC patients express the highest levels of co-inhibitory molecules compared to Treg cells isolated from tumor adjacent tissues or from peripheral blood of cancer patients, which is in consistent with the enhanced immunosuppressive function of these co-inhibitory molecules. Moreover, the number of Treg cells and their functional surface molecules increased during the progression of lung cancer. Elevated plasma levels of TGF-β and IL-10 in NSCLC patients were also observed in NSCLC patients compared to that in healthy volunteers. Our findings further support the role of Treg cells in the tumor microenvironments in NSCLC patients.     

Relationship between Th17 immune response and cancer

Cancer is the second leading cause of death worldwide and epidemiological projections predict growing cancer mortality rates in the next decades. Cancer has a close relationship with the immune system and, although Th17 cells are known to play roles in the immune response against microorganisms and in autoimmunity, studies have emphasized their roles in cancer pathogenesis. The Th17 immune response profile is involved in several types of cancer including urogenital, respiratory, gastrointestinal, and skin cancers. This type of immune response exerts pro and antitumor functions through several mechanisms, depending on the context of each tumor, including the protumor angiogenesis and exhaustion of T cells and the antitumor recruitment of T cells and neutrophils to the tumor microenvironment. Among other factors, the paradoxical behavior of Th17 cells in this setting has been attributed to its plasticity potential, which makes possible their conversion into other types of T cells such as Th17/Treg and Th17/Th1 cells. Interleukin (IL)-17 stands out among Th17-related cytokines since it modulates pathways and interacts with other cell profiles in the tumor microenvironment, which allow Th17 cells to prevail in tumors. Moreover, the IL-17 is able to mediate pro and antitumor processes that influence the development and progression of various cancers, being associated with variable clinical outcomes. The understanding of the relationship between the Th17 immune response and cancer as well as the singularities of carcinogenic processes in each type of tumor is crucial for the identification of new therapeutic targets.     

Mature dendritic cells enriched in regulatory molecules may control regulatory T cells and the prognosis of head and neck cancer

We previously reported that regulatory T (Treg) cells expressing CTLA-4 on the cell surface are abundant in head and neck squamous cell carcinoma (HNSCC). The role of expanded Treg cells in the tumor microenvironment of HNSCC remains unclear. In this study, we reveal that the tumor microenvironment of HNSCC is characterized by the high expression of genes related to Treg cells, dendritic cells (DCs), and interleukin (IL)-17-related molecules. Increased expression of IL17A, IL17F, or IL23A contributes to a favorable prognosis of HNSCC. In the tumor microenvironment of HNSCC, IL23A and IL12B are expressed in mature dendritic cells enriched in regulatory molecules (mregDCs). The mregDCs in HNSCC are a migratory and mature phenotype; their signature genes strongly correlate with Treg signature genes in HNSCC. We also observed that IL17A was highly expressed in Th17 cells and exhausted CD8⁺ T cells in HNSCC. These data suggest that mregDCs in HNSCC may contribute to the prognosis by balancing Treg cells and effector T cells that produce IL-17. Targeting mregDCs may be a novel strategy for developing new immune therapies against HNSCC.     

调节性T细胞与肿瘤

调节性T（regulatory T, Treg）细胞是一群具有抑制其他免疫细胞功能的负调控细胞，包括CD4+ Treg、CD8+ Treg、NKT Treg 和双阴性（double negative，DN）Treg细胞等四大类。研究显示，肿瘤微环境中Treg细胞数量升高，且这些升高的 Treg细胞能抑制抗肿瘤免疫、降低肿瘤免     

Toll-like receptors and immune regulation: implications for cancer therapy

Toll-like receptors (TLRs) function as pathogen pattern recognition molecules that sensor and initiate innate and adaptive immune responses against microbes and cancer cells. Recognition of pathogen-derived ligands by TLRs expressed on many types of cells, including dendritic cells and T cells, triggers the nuclear factor (NF)-kappaB and type-1 interferon pathways, leading to the production of proinflammatory cytokines that are essential in stimulating CD4(+) T cells to differentiate to T helper (Th) 1, Th2 Th17 and regulatory T (Treg) cells. Recent studies indicate that Treg cells play a critical role in suppressing immune responses and inducing immune tolerance to cancer and infectious diseases. Of particular interest, the human TLR8 signaling pathway is essential for reversing the suppressive function of Treg cells. Thus, TLRs regulate cancer immunity and tolerance through innate immune responses mediated by Treg, dendritic and other immune cells. In this review, we focus on the current understanding of TLRs and Treg cells with emphasis on their roles in cancer immunity. Related information on non-TLR immune receptors will be briefly discussed.     

调节性T细胞与肺癌关系的研究进展

 CD+4 CD+25 Foxp3+ 调节性T（Treg）细胞是抑制性T细胞的一种亚群,能够强有力地抑制效应T淋巴细胞的活化、增生及功能,Treg细胞在防止自身免疫、介导移植耐受等方面发挥着重要作用。Treg细胞在肺癌组织及患者外周血中含量明显增高,与肺癌的临床分期及肺癌类型密切相关。Treg细胞对于肺癌临床诊断以及治疗有重要意义。     

调节性T细胞在多发性骨髓瘤中的研究进展

调节性T细胞（Treg细胞）是一群具有免疫抑制功能的细胞,在肿瘤免疫中有着重要作用.文章对Treg细胞的基本特征、多发性骨髓瘤（MM）中Treg细胞的变化、MM中Treg细胞的作用方式及治疗对Treg细胞影响等的研究进展作一综述.     

Th17细胞与肿瘤

Th17细胞是一类CD4+效应T细胞.研究发现Th17细胞及其相关细胞因子存在于许多肿瘤中,并在炎症相关性肿瘤中发挥重要作用,但对Th17细胞在肿瘤微环境中的分化表达、免疫调控机制及功能效应仍不明确.     

CD4+CD25+调节性T细胞对晚期肺癌患者免疫抑制作用的研究

目的 探讨Treg及Th1/Th2类细胞因子在晚期肺癌肿瘤免疫抑制中的作用.方法 选取100例初治晚期肺癌患者及50例健康自愿者.采用流式细胞术检测其外周血中Treg、Th1类细胞因子(IFN-γ、IL-2、TNF-a)、Th2类细胞因子(IL-4、IL-6、IL-10)水平,同时分析CD4+CD25+Treg与Th1/Th2类细胞因子之间的相关性.结果 ①晚期肺癌患者外周血中Treg为(11.12±5.83)%,高于健康对照组(7.46±3.07)%,差异有统计学意义(P=0.003);②化疗前肺癌患者外周血中Treg为(11.12±5.83)%,明显高于化疗后(6.45±3.74)%,差异有统计学意义(P<0.001);③晚期肺癌患者与正常对照组Th1/Th2类细胞因子水平分别为:IFN-γ(8.56±3.62 vs 10.79±3.27,P=0.049)、IL-2(8.48±2.87 vs 10.22±4.03,P=0.03)、TNF-a(6.18±2.67vs8.14±2.87,P=0.007)、IFN-γ/IL-4(3.33±1.44 vs 4.09±1.00,P=0.028)、IL-4(3.17±1.19 vs 2.45±0.43,P<0.001)、IL-6(3.88±2.08 vs 2.33±0.88,P<0.001)、IL-10(3.64±1.73 vs 2.54±1.08,P=0.008),其中Th2类因子水平明显升高,差异有统计学意义(P均<0.05);④CD4+CD25+Treg与Th1类细胞因子IFN-γ、TNF-a、IL-2及IL-6无相关性(P均>0.05);与Th1/Th2(γ=-0.273,P=0.003)呈负相关;与Th2类细胞因子IL-4(γ=0.237,P=0.009)、IL-10(0.626,P<0.001)呈正相关(P均<0.05).结论 晚期肺癌患者CD4+CD25+Treg、Th2类细胞因子水平显著升高,Th1类细胞因子水平下降,它们共同导致肿瘤患者免疫抑制及肿瘤进展,监测其水平变化有助于判断肺癌患者疗效、预后,有效调控CD4+CD25+Treg及负性细胞因子水平可能是治疗肺癌的一个新策略.     

恶性胸腔积液中CD4+T细胞的研究进展

细胞免疫是人体免疫系统的重要组成部分,主要由CD8＋细胞毒T细胞及CD4＋辅助性T细胞介导机体免疫反应,其中CD4＋T细胞又包括多个亚群,如Th1、Th2细胞,目前又发现了新的亚群如Treg、Th17、Th9,均不同程度参与了疾病的免疫过程,而对于肿瘤的抑制或促进作用机制尚不清楚。本综述收集了恶性胸腔积液中有关CD4＋T亚群变化及可能机制的最新资料,分析其在肿瘤中的特性和作用以了解在肿瘤局部微环境的效应机制,为肿瘤的诊断治疗提供新的靶点。