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PD-L1 is a direct target of cancer-foxp3 in pancreatic ductal adenocarcinoma(PDAC),and combined immunotherapy with antibodies against PD-L1 and CCL5 is effective in the treatment of PDAC

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2043-2054页

作者： Xiuchao Wang Xin Li Xunbin Wei Haiping Jiang Chungen Lan Shengyu Yang Han Wang Yanhui Yang Caijuan Tian Zanmei Xu Jiangyan Zhang Jihui Hao He Ren Department of Gastroenterology Center of Tumor Immunology and CytotherapyThe Affiliated Hospital of Qingdao University266003 QingdaoChina Department of Cellular and Molecular Physiology Penn State College of MedicineHersheyPA 17033USA Department of Pancreatic Cancer Tianjin Medical University Cancer Institute and Hospital300060 TianjinChina Department of Geriatric Dentistry Beijing Laboratory of Biomedical MaterialsPeking University School and Hospital of Stomatologyand Biomedical Engineering DepartmentPeking University100081 BeijingChina Department of Applied Statistics College of ScienceHebei University of Technology300401 TianjinChina NHC Key Laboratory of Hormones and Development(Tianjin Medical University) Tianjin Key Laboratory of Metabolic DiseasesTianjin Medical University Chu Hsien-I Memorial Hospital&Tianjin Institute of Endocrinology300134 TianjinChina Tianjin Marvel Medical Laboratory Tianjin Marvelbio Technology Co.Ltd300381 TianjinChina

High expression of PD-L1 marks the poor prognosis of pancreatic ductal adenocarcinomas(PDAC).However,the regulatory mechanism of PD-L1 remains elusive.We recently reported that cancer Forkhead box protein 3(Cancer-foxp3 or C-foxp3)promoted immune evasion of PDAC by recruiting Treg cells into PDAC via upregulation of CCL5.In this study,we confirmed that PD-L1 was overexpressed in PDAC samples from two independent cohorts of patients with radical resection.Moreover,C-foxp3 was colocalized and correlated with the expression of PD-L1 in tumor cells at the mRNA and protein levels,and this finding was confirmed by the The Cancer Genome Atlas(TCGA)database.Chromatin immunoprecipitation(ChIP)revealed that C-foxp3 directly bound to the promoter region of PD-L1 in pancreatic cancer cells.Furthermore,overexpression of C-foxp3 activated the luciferase reporter gene under the control of the PD-L1 promoter.However,mutation of the binding motif-a completely reversed the luciferase activity.In addition,C-foxp3-induced upregulation of PD-L1 effectively inhibited the activity of CD8+T cells.Based on our recent finding that the CCL-5 antibody achieved a better response to PDAC models with high C-foxp3 levels,we further demonstrated that the PD-L1 antibody strengthened the antitumor effect of CCL-5 blockade in xenograft and orthotopic mouse models with high C-foxp3 levels.In conclusion,C-foxp3 directly activates PD-L1 and represents a core transcription factor that mediates the immune escape of PDAC.Combined blockade of PD-L1 and CCL-5 may provide an effective therapy for patients with PDAC that have high C-foxp3 levels.

关键词： CCL5 foxp3 adenocarcinoma

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Relatively Increased Number of Liver foxp3^+ Regulatory T Cells against Hepatic Lesions in Murine Lupus

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2011年第4期31卷 476-481页

作者：余立凯黄安斌王玮炜杜戎沈凌汛侯晓华 Department of Rheumatology Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of Gastroenterology Union HospitalTongji Medical CollegeHuazhong University of Science and Technology

Systemic lupus erythematosus（SLE） is a multiple organ autoimmune disorder,including the liver,but the possible reason in impairment in the liver is still unclear.Our present study assessed alterations of transcription factor foxp3＋ regulatory T cells（Tregs） and several other immune molecules [programmed cell death 1 and its ligand（PD1 and PD-L1）,and interleukin 10（IL-10） and transform growth factor β（TGF-β）] in the liver and other major organs of lupus-prone BXSB mice by flow cytometry,real-time quantitative reverse transcription PCR,and enzyme-linked immunosorbent assay.Results showed that both frequency and number of foxp3＋ Tregs were dramatically reduced in the thymus,spleen and kidney of the BXSB mice（P0.05）,but those in the liver were kept in nearly normal range,when compared to negative control C57BL/6 mice.In comparison to control mice,the mRNA levels of foxp3,PD1 and PD-L1 were significantly decreased in the kidneys of BXSB mice（P0.05）,but there was no significant difference in the livers of the BXSB mice（P0.05）.Protein levels of IL-10 and TGF-β in serum showed no significant difference between BXSB and C57BL/6 mice,but were significantly increased in the kidneys and livers of BXSB mice as compared with those in C57BL/6 mice（P0.05）.These results suggest that reduced foxp3＋ Tregs are involved in the pathogenesis of SLE in BXSB mice,and relatively higher number of these cells in the livers than in the other target organs could constitute a protective mechanism against hepatic lesions in lupus-prone mice,which may provide insights into development of new therapeutic approaches in SLE patients.

关键词： foxp3 hepatic lesion lupus BXSB mice

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Effect of Yupingfeng granules on HA and foxp3^+ Treg expression in patients with nasopharyngeal carcinoma

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Asian Pacific Journal of Tropical Medicine 2015年第8期8卷 662-664页

作者： Ji-Hong Huang Zhong-Lin Mu Xue-Jun Zhou Qiong-Lian Huang Feng Gao Xi Chen Hainan Medical University

Objective: To investigate the effect of Yupingfeng on hyaluronic acid(HA) and foxp3+ Treg in patients with nasopharyngeal carcinoma. Methods: A total of 58 cases of nasopharyngeal carcinoma were divided into two groups, 30 cases in the treatment group, 28 cases in the control group. Patients in two groups were treated with synchronous radiotherapy and chemotherapy treatment, the treatment group was treated with the Yupingfeng granules through oral administration, 10 g/time, tid for 2 courses. The serum foxp3+ Treg markers of each group were detected by flow cytometry assay before treatment and after treatment, and the level of HA in serum was detected by radio immunoassay. Results: After radiotherapy and chemotherapy, the contents of foxp3+ Treg and HA were significantly decreased in two groups(Pfoxp3+ Treg and HA(Pfoxp3+ Treg and HA in nasopharyngeal carcinoma patients. Yupingfeng can also effectively reduce the side effect due to radiation and chemotherapy.

关键词： Nasopharyngeal carcinoma Yupingfeng foxp3 Treg HA

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三子颗粒治疗大鼠慢性湿疹模型皮损的作用机制研究

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中华中医药学刊 2024年

作者：陈兴丛培玮孙巍关洪全李忻红王希子侯殿东田静辽宁中医药大学辽宁中医药大学附属医院沈阳市第七人民医院湖州师范学院

目的应用三子颗粒治疗大鼠慢性湿疹模型，探讨其外治慢性湿疹的作用机制。方法 40只SD雄性大鼠，随机分为正常组、模型组、三子颗粒组、青鹏软膏组，每组10只。以二硝基氯苯丙酮溶液制备大鼠慢性湿疹模型，模型组湿敷生理盐水，三子颗... 详细信息

目的应用三子颗粒治疗大鼠慢性湿疹模型，探讨其外治慢性湿疹的作用机制。方法 40只SD雄性大鼠，随机分为正常组、模型组、三子颗粒组、青鹏软膏组，每组10只。以二硝基氯苯丙酮溶液制备大鼠慢性湿疹模型，模型组湿敷生理盐水，三子颗粒组湿敷三子颗粒洗剂，青鹏软膏组外用青鹏软膏。通过皮损评分评价疗效，苏木精－伊红染色法（hematoxylin-eosinstaining，HE）染色观察皮肤组织形态学变化，甲苯胺蓝染色法观察皮肤组织肥大细胞数量，免疫组化技术法检测皮损组织干扰素γ（interferongamma，IFN-γ）、白介素4（interleukin-4，IL-4）的蛋白表达，Westernblot法检测皮损组织中白介素17（interleukin-17，IL-17）、叉头样转录因子3（forkheadtranscriptionfactor3，foxp3）、磷酸化p38丝裂原活化蛋白激酶（phosphorylated-p38mitogenactivatedproteinkinase，p-p38MAPK）、p38丝裂原活化蛋白激酶（p38mitogenactivatedproteinkinase，p38MAPK）、磷酸化核转录因子-κBp65（phosphorylated-nuclearfactor-κBp65，p-NF-κBp65）、核转录因子-κBp65（nuclearfactor-κBp65，NF-κBp65）的蛋白表达含量。结果模型组大鼠表皮病理表现出角化过度、角化不全，颗粒层和棘层显著增厚，胶原纤维变粗；模型组肥大细胞数量显著升高，IFN-γ、foxp3蛋白表达降低、IL-4、IL-17、p-p38MAPK/p38MAPK、p-NF-κBp65/NF-κBp65蛋白表达升高。与模型组比较，三子颗粒组的皮损评分在第6天、8天、10天均显著减少，病理改变减轻，IFN-γ、foxp3表达明显增高（P＜0.01）、IL-4、p-p38MAPK/p38MAPK、p-NF-κBp65/NF-κBp65表达均显著降低（P＜0.05和P＜0.01），IL-17表达下降，但差异无统计学意义（P>0.05）。结论三子颗粒可通过抑制肥大细胞过度增生，上调IFN-γ、foxp3的蛋白水平，降低IL-4、IL-17、p-p38MAPK/p38MAPK、p-NF-κBp65/NF-κBp65的蛋白水平，发挥其对慢性湿疹的治疗作用，初步揭示了三子颗粒外治慢性湿疹的作用机制。

关键词：慢性湿疹三子颗粒 IFN-γ IL-4 IL-17 foxp3 p38MAPK/NF-κBp65

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重度子痫前期孕妇胎盘组织中Treg细胞及其相关因子的表达意义研究

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中国妇产科临床杂志 2024年第3期25卷 196-199页

作者：刘涛李兰贵州中医药大学第一附属医院重症医学科贵阳550001

目的探讨Treg细胞及其相关因子在重度子痫前期(SPE)孕妇胎盘组织中的表达和意义。方法纳入贵州中医药大学第一附属医院重症医学科2020年1月至2022年1月收治的74例SPE患者(SPE组)和本院同期75例正常足月生产的产妇(对照组)作为研究对象... 详细信息

目的探讨Treg细胞及其相关因子在重度子痫前期(SPE)孕妇胎盘组织中的表达和意义。方法纳入贵州中医药大学第一附属医院重症医学科2020年1月至2022年1月收治的74例SPE患者(SPE组)和本院同期75例正常足月生产的产妇(对照组)作为研究对象。收集研究对象基线资料及实验室检查数据,检测研究对象外周血CD4+CD25+Treg细胞的表达水平,荧光定量聚合酶链反应(PCR)检测外周血Treg细胞转录因子foxp3 mRNA、转化生长因子β1(TGF-β1)表达水平,采用蛋白印迹法(Western blot)检测胎盘组织中foxp3、TGF-β1蛋白表达水平。结果SPE组患者血清CD4+CD25+Treg占比低于对照组;SPE组患者血清IL-10、TGF-β1水平均高于对照组(Pfoxp3 mRNA表达水平低于对照组(Pfoxp3蛋白表达量低于对照组,TGF-β蛋白表达量高于对照组;SPE患者外周血TGF-β1水平与胎盘组织TGF-β1蛋白水平呈正相关关系(r=0.645,Pfoxp3、TGF-β1)的表达均发生改变。

关键词：重度子痫前期胎盘组织 Treg细胞 foxp3 转化生长因子β

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Co-expression of HBZ,TAX and foxp3 and HTLV-1-associated myelopathy/tropical spastic paraparesis development in HTLV-1-infected individuals:A systematic review

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Asian Pacific Journal of Tropical Medicine 2021年第8期14卷 333-340页

作者： Ana Carolina Marinho Monteiro Lima Greice Carolina Santos da Silva Fernanda Khouri Barreto Filipe Ferreira de Almeida Rego Luana Leandro Gois Luciane Amorim Santos Catholic University of Salvador SalvadorBahiaBrazil Multidisciplinary Institute in Health Federal University of BahiaVitoria da ConquistaBahiaBrazil Bahia School of Medicine and Public Health SalvadorBahiaBrazil Postgraduate Program in Health Sciences Faculty of Medicine of BahiaFederal University of BahiaSalvadorBahiaBrazil

Human T-cell lymphotropic virus type 1(HTLV-1)is associated with the development of HTLV-1-associated myelopathy/tropical spastic paraparesis(HAM/TSP).It has been reported that the HTLV-1 proteins(specifically TAX and HBZ)can modulate foxp3,resulting in an immune imbalance that can favor the progression of HAM/TSP.This review aims to summarize the literature in order to clarify the relationship between the expression of HTLV-1 m RNAs and/or viral proteins(TAX and HBZ)with the expression of mRNA and/or protein foxp3 and their correlation with HAM/TSP development.This systematic review was conducted according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis.The search strategy was performed on the Medical Literature Analysis and Retrieval System Online and Latin American and Caribbean Literature in Health Sciences Platform using subject descriptors.After screening,six articles were included in this review.The studies suggested that TAX and HBZ have a directly proportional correlation with foxp3 in individuals with HAM/TSP,which also presented an increased expression of foxp3 compared to asymptomatic controls and/or healthy donors.This systematic review indicates that TAX and HBZ can interact with foxp3 and that interaction may influence HAM/TSP development.

关键词： HTLV-1 HTLV-1-associated myelopathy/tropical spastic paraparesis(HAM/TSP) foxp3 HBZ TAX

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非小细胞肺癌血浆天然CD25抗体及foxp3抗体的表达变化及其作为诊断标志物的探讨

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中国免疫学杂志 2022年第1期38卷 80-85页

作者：赵欢张萱李庆海(指导) 青岛大学附属青岛市市立医院内分泌科青岛266071 吉林大学第二医院吉林省分子与遗传学重点实验室长春130031 青岛大学附属青岛市市立医院呼吸科青岛266071

目的:探讨天然CD25和foxp3抗体在非小细胞肺癌(NSCLC)患者血浆表达变化的临床意义及其作为诊断标志物的潜能。方法:选取青岛大学附属青岛市立医院胸外科首次确诊且未经任何治疗的NSCLC患者200例及同期性别、年龄、吸烟史相匹配的健康志... 详细信息

目的:探讨天然CD25和foxp3抗体在非小细胞肺癌(NSCLC)患者血浆表达变化的临床意义及其作为诊断标志物的潜能。方法:选取青岛大学附属青岛市立医院胸外科首次确诊且未经任何治疗的NSCLC患者200例及同期性别、年龄、吸烟史相匹配的健康志愿者190例,收集两组血液样本。基于CD25及foxp3分子结构,利用表位预测软件(http://***)设计并合成3条线性抗原肽(即CD25a、CD25b、foxp3)并外送化工公司合成,通过自行建立的优化ELISA检测方法,检测NSCLC患者及健康对照组血浆CD25及foxp3抗体的表达水平,并分析CD25及foxp3抗体的表达与临床病理特征之间的关系。同时绘制ROC曲线,评估CD25及foxp3抗体对不同TNM分期NSCLC的诊断价值。结果:NSCLCⅡ~Ⅳ期患者血浆CD25a、foxp3抗体的表达较健康对照组显著增加(0.66±0.18 vs 0.52±0.17,P3 vs 0.53±0.25,P37±0.21 vs 0.43±0.22,P0.05)。CD25b抗体的表达与性别、年龄、肿瘤分化程度有关(P均0.05),而foxp3抗体的表达仅与肿瘤分化程度有关(Pfoxp3抗体诊断NSCLC的效能评估,CD25a曲线下面积为0.727(95%CI:0.677~0.778),最佳截断值为0.55,敏感度为77%,特异度为64%;CD25b曲线下面积为0.601(95%CI:0.545~0.657),最佳截断值为0.35,敏感度为62%,特异度为57%;foxp3曲线下面积为0.613(95%CI:0.557~0.669),最佳截断值为0.54,敏感度为58%,特异度为65%。结论:检测CD25a天然抗体可辅助NSCLC的早期诊断;血浆CD25b天然抗体在早期NSCLC(Ⅰ+Ⅱ期)表达降低,对预测早期NSCLC有一定价值。

关键词：天然抗体 CD25 foxp3 非小细胞肺癌

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Correction to:TGF-beta1 gene-modified,immature dendritic cells delay the development of inflammatory bowel disease by inducing CD4(+)foxp3(+)regulatory T cells

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Cellular & Molecular Immunology 2020年第2期17卷 190-191页

作者： Zhijian Cai Wei Zhang Min Li Yinpu Yue Fei Yang Lei Yu Xuetao Cao Jianli Wang Institute of Immunology Zhejiang University School of Medicine Hangzhou China. Institute of Immunology and National Key Laboratory of Medical Immunology Second Military Medical University Shanghai China. Institute of Immunology Zhejiang University School of Medicine Hangzhou China. jlwang@***.

Correction to:Cellular&Molecular Immunology https://***/10.1038/cmi.2009.107,published online 18 January 2010 Zhijian Cai,Wei Zhang,Min Li,Yinpu Yue,Fei Yang,Lei Yu,Xuetao Cao&Jianli Wang TGF-β1 gene-modified,immature dendritic cells delay the development of inflammatory bowel disease by inducing CD4^(+)foxp3^(+)regulatory T cells.Cell Mol Immunol.2010 Jan;7(1):35-43.

关键词： foxp3 Immunol Immunology

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Role of foxp3 in Immunohistochemical Expression in Preeclampsia

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Open Journal of Obstetrics and Gynecology 2023年第4期13卷 699-711页

作者： Malames M. Faisal Hesham M. Harb Fatma S. Hafez Mohamed T. Elsaid Department of Obstetrics and Gynecology Faculty of Medicine Ain Shams University Cairo Egypt Department of Pathology Faculty of Medicine Ain Shams University Cairo Egypt

Background: foxp3 gene variants have been linked to endometriosis, infertility, and autoimmune illnesses, according to numerous researches. Maternal sensitivity to the PE gene and the genetic variations of foxp3 has not been thoroughly investigated. Objective: Investigation of the immune-histochemical expression of foxp3 in placental tissue of PE patients. Methods: A total of 26 pre-eclamptic women as a case and 26 ethnically matched healthy pregnant women as a control group aged between 18 and 40 years old of different gravidity and parity referred to the labor ward for delivery either by vaginal delivery or cesarean section was enrolled to investigate the immunohistochemical expression of foxp3 in placental tissue of PE patients. Results: Lower expression of foxp3 IHC was statistically significant and noted in the group of preeclampsia compared to the healthy control group. Lower gestational age at delivery and a higher percentage of cesarean section were statistically significant and noted in the group of preeclampsia compared to the healthy control group. Conclusion: In comparison to the healthy control group, preeclampsia patients had statistically significantly lower foxp3 IHC expression, and foxp3 polymorphism was associated with the development of PE. Our findings can serve as a guide for statistical analyses and functional investigations that are more in-depth.

关键词： foxp3 Immunohistochemical Expression Preeclampsia

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foxp3与宫颈癌发病风险及预后生物信息学

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中国老年学杂志 2022年第19期42卷 4662-4666页

作者：石凤王俊利董明右庞晓霞李光景韦莹慧右江民族医学院附属医院生殖医学中心广西百色533000 右江民族医学院医学检验学院临床血液学与形态学教研室

目的旨在通过生物信息学探讨叉头/翼状螺旋转录家族因子(foxp)3对宫颈癌发病风险及其预后的影响。方法从癌症基因组图谱(TCGA)数据库中下载泛癌临床信息。通过R3.6.0“ggpubr”包分析foxp3在泛癌中的表达,采用COX回归计算foxp3表达水平... 详细信息

目的旨在通过生物信息学探讨叉头/翼状螺旋转录家族因子(foxp)3对宫颈癌发病风险及其预后的影响。方法从癌症基因组图谱(TCGA)数据库中下载泛癌临床信息。通过R3.6.0“ggpubr”包分析foxp3在泛癌中的表达,采用COX回归计算foxp3表达水平与宫颈癌的总体生存率,采用Spearman相关检验计算foxp3与宫颈癌肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)和免疫浸润细胞的相关性,并通过UALCAN数据库分析foxp3表达水平对宫颈癌临床特征的影响。结果相对于正常组织,foxp3在宫颈癌等多种肿瘤中的表达水平升高,并与宫颈癌患者年龄、种族、体重、肿瘤分级和淋巴结转移等临床特征存在相关性。相对于foxp3低表达组,foxp3高表达的宫颈癌患者总体生存率更好(Pfoxp3表达水平与宫颈癌免疫细胞浸润有关,但未发现foxp3与TMB和MSI的相关性。结论过生物信息学发现foxp3与宫颈癌的发病风险和预后有关。

关键词： foxp3 宫颈癌预后生物信息学

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