CD4+CD25+Foxp3+Treg细胞调控肿瘤免疫抑制微环境的研究进展

doi:10.11904/j.issn.1002-3070.2016.06.016

实用肿瘤学杂志 ›› 2016, Vol. 30 ›› Issue (6): 555-559.doi: 10.11904/j.issn.1002-3070.2016.06.016

CD4⁺CD25⁺Foxp3⁺Treg细胞调控肿瘤免疫抑制微环境的研究进展

刘珈杞，刘耀华，陈鑫，综述，赵世光，审校

哈尔滨医科大学附属第一医院(哈尔滨 150001)

收稿日期:2016-08-09 出版日期:2016-12-31 发布日期:2016-12-27
通讯作者: 赵世光,E-mail:guangsz@hotmail.com
作者简介:刘珈杞，男，(1988-)，硕士研究生，从事神经胶质瘤治疗的研究
基金资助:
国家自然科学基金项目(81272788);国家自然科学基金项目(81372701)

Research progress of CD4⁺CD25⁺Foxp3⁺ regulatory T cells in tumor immunosuppressive microenvironment

LIU Jiaqi,LIU Yaohua,CHEN Xin,ZHAO Shiguang

The First Affiliated Hospital of Harbin Medical University,Harbin 150001,China

Received:2016-08-09 Online:2016-12-31 Published:2016-12-27

摘要/Abstract

摘要： 目的 CD4⁺CD25⁺Foxp3⁺调节性T细胞(Treg)是肿瘤免疫抑制微环境的主要组成部分，其在肿瘤的免疫抑制微环境中分泌IL-10、IL-35、TGF-β1和FGL2等细胞因子发挥免疫抑制作用。Treg细胞抑制CD4⁺T、CD8⁺T淋巴细胞和NK细胞，进而抑制特异性抗肿瘤免疫反应使肿瘤细胞更容易逃避免疫监视。进一步研究Treg细胞在肿瘤免疫中的作用机制，对深入了解恶性肿瘤的发病机制及免疫治疗具有重要的理论意义。此外，Treg细胞及其分泌的细胞因子在肿瘤治疗和预后评估等方面也具有广阔的临床应用前景。

关键词: 调节性T细胞, 肿瘤逃逸, 免疫抑制微环境

Abstract: CD4⁺CD25⁺Foxp3⁺regulatory T cells(Tregs)are essential for tumor immunosuppressive microenvironment and secrete some inhibitory cytokines IL-10,IL-35,TGF-β1 and FGL2 which are key mediators of Treg immunosuppressive function.Tregs have been shown to be important contributors to the tumor escape immunosurveillance and play a critical role in the induction of suppression to CD4⁺T,CD8⁺T and NK cell,and suppression of specific anti-tumor immunity.Further research of the role of Tregs in tumor immunosuppressive microenvironment is important to understand malignant tumor pathogenetic and immunological therapeutics.In addition,Tregs and inhibitory cytokines become more critical for clinical applications,prognosis evaluation and therapies.

Key words: Regulatory T cell, Tumor escape, Immunosuppression microenvironment

中图分类号:

R730.2

刘珈杞，刘耀华，陈鑫，综述，赵世光，审校. CD4⁺CD25⁺Foxp3⁺Treg细胞调控肿瘤免疫抑制微环境的研究进展[J]. 实用肿瘤学杂志, 2016, 30(6): 555-559.

LIU Jiaqi,LIU Yaohua,CHEN Xin,ZHAO Shiguang. Research progress of CD4⁺CD25⁺Foxp3⁺ regulatory T cells in tumor immunosuppressive microenvironment[J]. PRACTICAL ONCOLOGY JOURNAL, 2016, 30(6): 555-559.

参考文献

1 Chen X,Du Y,Lin X,et al.CD4⁺CD25⁺ regulatory T cells in tumor immunity[J].Int Immunopharmacol,2016,34:244-249.
2 Du Y,Chen X,Lin XQ,et al.Tumor-derived CD4⁺CD25⁺ Tregs inhibit the maturation and antigen-presenting function of dendritic cells[J].Asian Pac J Cancer Prev,2015,16(7):2665-2669.
3 Subramaniam DS,Liu SV,Giaccone G.Novel approaches in cancer immunotherapy[J].Discov Med,2016,21(116):267-274.
4 Adeegbe DO,Nishikawa H.Natural and induced T regulatory cells in cancer[J].Front Immunol,2013,4(190):1-14.
5 Xu A,Liu Y,Chen W,et al.TGF-beta-induced regulatory T cells directly suppress B cell responses through a noncytotoxic mechanism[J].J Immunol,2016,196(9):3631-3641.
6 Qin FX.Dynamic behavior and function of Foxp3+ regulatory T cells in tumor bearing host[J].Cell Mol Immunol,2009,6(1):3-13.
7 Williams LM,Rudensky AY.Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3[J].Nat Immunol,2007,8(3):277-284.
8 Rudensky AY,Campbell DJ.In vivo sites and cellular mechanisms of T reg cell-mediated suppression[J].J Exp Med,2006,203(3):489-492.
9 Vignali D.How many mechanisms do regulatory T cells need?[J].Eur J Immunol,2008,38(4):908-911.
10 Qureshi OS,Zheng Y,Nakamura K,et al.Trans-endocytosis of CD80 and CD86:a molecular basis for the cell-extrinsic function of CTLA-4[J].Science,2011,332(6029):600-603.
11 Shevach EM.Mechanisms of foxp3+ T regulatory cell-mediated suppression[J].Immunity,2009,30(5):636-645.
12 Cribbs AP,Kennedy A,Penn H,et al.Treg cell function in rheumatoid arthritis is compromised by ctla-4 promoter methylation resulting in a failure to activate the indoleamine 2,3-dioxygenase pathway[J].Arthritis Rheumatol,2014,66(9):2344-2354.
13 Chruscinski A,Sadozai H,Rojas-Luengas V,et al.Role of regulatory T rells(Treg)and the Treg effector molecule fibrinogen-like protein 2 in alloimmunity and autoimmunity[J].Rambam Maimonides Med J,2015,6(3):e0024.
14 Li JN,Li JX,Huang HL,et al.Influence of sirolimus-induced TGF-beta secretion on mouse Treg cell proliferation[J].Genet Mol Res,2015,14(4):18569-18579.
15 Fukumura D,Jain RK.Tumor microenvironment abnormalities:causes,consequences,and strategies to normalize[J].J Cell Biochem,2007,101(4):937-949.
16 Takeda Y,Marumo M,Nara H,et al.Selective induction of anti-inflammatory monocyte-platelet aggregates in a model of pulsatile blood flow at low shear rates[J].Platelets,2016,27(6):583-592.
17 Cantini G,Pisati F,Mastropietro A,et al.A critical role for regulatory T cells in driving cytokine profiles of Th17 cells and their modulation of glioma microenvironment[J].Cancer Immunol Immunother,2011,60(12):1739-1750.
18 Noori-Zadeh A,Mesbah-Namin SA,Bistoon-Beigloo S,et al.Regulatory T cell number in multiple sclerosis patients:A meta-analysis[J].Mult Scler Relat Disord,2016,5:73-76.
19 Gao YL,Chai YF,Qi AL,et al.Neuropilin-1(high)CD4(+)CD25(+)regulatory T cells exhibit primary negative immunoregulation in sepsis[J].Mediators Inflamm,2016,2016:7132158.
20 Wang S,Gao X,Shen G,et al.Interleukin-10 deficiency impairs regulatory T cell-derived neuropilin-1 functions and promotes Th1 and Th17 immunity[J].Sci Rep,2016,6:24249.
21 Shen P,Roch T,Lampropoulou V,et al.IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases[J].Nature,2014,507(7492):366-370.
22 Collison LW,Workman CJ,Kuo TT,et al.The inhibitory cytokine IL-35 contributes to regulatory T-cell function[J].Nature,2007,450(7169):566-569.
23 Wang Z,Liu JQ,Liu Z,et al.Tumor-derived IL-35 promotes tumor growth by enhancing myeloid cell accumulation and angiogenesis[J].J Immunol,2013,190(5):2415-2423.
24 Yu W,Ge M,Lu S,et al.Anti-inflammatory effects of interleukin-35 in acquired aplastic anemia[J].Cytokine,2015,76(2):409-416.
25 Turnis ME,Sawant DV,Szymczak-Workman AL,et al.Interleukin-35 limits anti-tumor immunity[J].Immunity,2016,44(2):316-329.
26 Hu J,Yan J,Rao G,et al.The duality of fgl2-secreted immune checkpoint regulator versus membrane-associated procoagulant:therapeutic potential and implications[J].Int Rev Immunol,2014,28(3):1-15.
27 Shalev I,Selzner N,Helmy A,et al.The role of fgl2 in the pathogenesis and treatment of hepatitis C virus infection[J].Rambam Maimonides Med J,2010,1(1):e0004.
28 Shalev I,Wong KM,Foerster K,et al.The novel CD4+CD25+ regulatory T cell effector molecule fibrinogen-like protein 2 contributes to the outcome of murine fulminant viral hepatitis[J].Hepatology,2009,49(2):387-397.
29 Zhao Z,Yang C,Wang L,et al.The regulatory T cell effector soluble fibrinogen-like protein 2 induces tubular epithelial cell apoptosis in renal transplantation[J].Exp Biol Med(Maywood),2014,239(2):193-201.
30 Antonioli L,Pacher P,Vizi ES,et al.CD39 and CD73 in immunity and inflammation[J].Trends Mol Med,2013,19(6):355-367.
31 Dwyer KM,Deaglio S,Gao W,et al.CD39 and control of cellular immune responses[J].Purinergic Signal,2007,3(1/2):171-180.
32 Regateiro FS,Cobbold SP,Waldmann H.CD73 and adenosine generation in the creation of regulatory microenvironments[J].Clin Exp Immunol,2013,171(1):1-7.
33 Ohta A,Sitkovsky M.Extracellular adenosine-mediated modulation of regulatory T cells[J].Front Immunol,2014,5(304):1-9.
34 Xu S,Shao QQ,Sun JT,et al.Synergy between the ectoenzymes CD39 and CD73 contributes to adenosinergic immunosuppression in human malignant gliomas[J].Neuro Oncol,2013,15(9):1160-1172.
35 Almahariq M,Mei FC,Wang H,et al.Exchange protein directly activated by cAMP modulates regulatory T-cell-mediated immunosuppression[J].Biochem J,2015,465(2):295-303.
36 Behairy BE,El-Araby HA,Abd El Kader HH,et al.Assessment of intrahepatic regulatory T cells in children with autoimmune hepatitis[J].Ann Hepatol,2016,15(5):682-690.
37 Ulges A,Witsch EJ,Pramanik G,et al.Protein kinase CK2 governs the molecular decision between encephalitogenic TH17 cell and Treg cell development[J].Proc Natl Acad Sci USA,2016,23[Epub ahead of print].
38 Akyol Erikci A,Karagoz B,Bilgi O.Regulatory T cells in patients with idiopathic thrombocytopenic purpura[J].Turk J Haematol,2016,33(2):153-155.
39 Chen G,Liang Y,Guan X,et al.Circulating low IL-23:IL-35 cytokine ratio promotes progression associated with poor prognosisin breast cancer[J].Am J Transl Res,2016,8(5):2255-2264.
40 Polz-Dacewicz M,Strycharz-Dudziak M,Dworzanski J,et al.Salivary and serum IL-10,TNF-alpha,TGF-beta,VEGF levels in oropharyngeal squamous cell carcinoma and correlation with HPV and EBV infections[J].Infect Agent Cancer,2016,11(1):45-51.

[1]	王东亮,戚宁,牟冠男,张月桂. 结直肠癌肿瘤微环境中调节性T细胞CD39、CD73亚群及二者双阳性亚群的临床意义[J]. 实用肿瘤学杂志, 2017, 31(4): 329-334.
[2]	张锐, 王智煜, 文孝婷综述, 赵晖审校. 肿瘤免疫抑制微环境对肿瘤免疫治疗作用的研究进展[J]. 实用肿瘤学杂志, 2016, 30(2): 167-171.
[3]	全丽娜,刘爱春,郭秀臣,李莲乔,贾垂明. B非霍奇金淋巴瘤患者Th17、Treg水平及Th17/Treg失衡的研究[J]. 实用肿瘤学杂志, 2013, 27(5): 400-405.
[4]	刘艳艳, 王东亮, 张艳桥. 调节性T细胞与恶性肿瘤的过继免疫治疗[J]. 实用肿瘤学杂志, 2012, 26(2): 173-177.
[5]	燕飞虎, 张艳桥, 王艳颖, 李志伟, 张纯慧, 娄长杰. 原发性肝细胞癌微环境中CD4⁺CD25⁺调节性T细胞分布与局部免疫的关系[J]. 实用肿瘤学杂志, 2010, 24(3): 201-203.

CD4⁺CD25⁺Foxp3⁺Treg细胞调控肿瘤免疫抑制微环境的研究进展

Research progress of CD4⁺CD25⁺Foxp3⁺ regulatory T cells in tumor immunosuppressive microenvironment

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 5

编辑推荐

Metrics

本文评价

CD4+CD25+Foxp3+Treg细胞调控肿瘤免疫抑制微环境的研究进展

Research progress of CD4+CD25+Foxp3+ regulatory T cells in tumor immunosuppressive microenvironment

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 5

编辑推荐

Metrics

本文评价

CD4⁺CD25⁺Foxp3⁺Treg细胞调控肿瘤免疫抑制微环境的研究进展

Research progress of CD4⁺CD25⁺Foxp3⁺ regulatory T cells in tumor immunosuppressive microenvironment