切换至 "中华医学电子期刊资源库"

中华诊断学电子杂志 ›› 2025, Vol. 13 ›› Issue (04) : 284 -288. doi: 10.3877/cma.j.issn.2095-655X.2025.04.013

综述

滤泡辅助性T细胞在恶性淋巴瘤中的研究进展
于梦凡1, 孙道萍2,()   
  1. 1272013 济宁医学院临床医学院
    2272011 济宁市第一人民医院血液内科
  • 收稿日期:2025-10-05 出版日期:2025-11-26
  • 通信作者: 孙道萍
  • 基金资助:
    山东省自然科学基金(ZR2020MH207,ZR2020MH251)

Research progress of T follicular helper cells in malignant lymphoma

Mengfan Yu1, Daoping Sun2,()   

  1. 1College of Clinical Medicine, Jining Medical University, Jining 272013, China
    2Department of Hematology, Jining No.1 People′s Hospital, Jining 272011, China
  • Received:2025-10-05 Published:2025-11-26
  • Corresponding author: Daoping Sun
引用本文:

于梦凡, 孙道萍. 滤泡辅助性T细胞在恶性淋巴瘤中的研究进展[J/OL]. 中华诊断学电子杂志, 2025, 13(04): 284-288.

Mengfan Yu, Daoping Sun. Research progress of T follicular helper cells in malignant lymphoma[J/OL]. Chinese Journal of Diagnostics(Electronic Edition), 2025, 13(04): 284-288.

滤泡辅助性T(Tfh)细胞是体液免疫的核心调控者,在生发中心的形成与B细胞的分化、成熟过程中发挥着不可或缺的作用。研究表明,Tfh细胞功能与数量异常在多种淋巴瘤发病中至关重要。除多种T细胞淋巴瘤,如血管免疫母细胞性T细胞淋巴瘤,直接起源于Tfh细胞外,在B细胞淋巴瘤中,Tfh细胞可通过多种共刺激信号及细胞因子支持恶性B细胞的存活并塑造免疫抑制微环境。本文综述Tfh细胞的生物学特性、分化调控及其在淋巴瘤中的作用及相关机制,讨论靶向Tfh细胞及相关通路的治疗策略,以期为淋巴瘤免疫治疗提供新思路。

As a master regulator of humoral immunity, T follicular helper (Tfh) cells play an indispensable role in germinal center formation and B cell differentiation and maturation. Dysregulation of Tfh cell function and quantity is critically implicated in the pathogenesis of various lymphomas. Beyond T cell lymphomas directly originating from Tfh cells, such as angioimmunoblastic T cell lymphoma, in B cell lymphoma, Tfh cells can support the survival of malignant B cells and shape an immunosupressive microenvironment via co-stimulatory signals and cytokines. This review summarizes the biology of Tfh cells, their roles and mechanisms in lymphomagenesis, and discusses therapeutic strategies targeting Tfh-related pathways, aiming to provide new perspectives for lymphoma immunotherapy.

[1]
Wang JNZheng GWu W,et al.Follicular helper T cells:emerging roles in lymphomagenesis[J].J Leukoc Biol2024116(1):54-63.DOI:10.1093/jleuko/qiad140.
[2]
Jain SMallick SRamteke P,et al.Neoplasms of follicular helper T-cells:an insight into the pathobiology [J].Am J Blood Res202212(3):64-81.
[3]
Breitfeld D, Ohl L, Kremmer E, et al. Follicular B helper T cells express CXC chemokine receptor 5,localize to B cell follicles,and support immunoglobulin production[J].J Exp Med2000192(11):1545-1552.DOI:10.1084/jem.192.11.1545.
[4]
Choi YSKageyama REto D,et al.ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6[J].Immunity201134(6):932-946.DOI:10.1016/j.immuni.2011.03.023.
[5]
Yu D, Rao S, Tsai LM, et al. The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment [J].Immunity200931(3):457-468.DOI:10.1016/j.immuni.2009.07.002.
[6]
Schmitt NBentebibel SEUeno H.Phenotype and functions of memory Tfh cells in human blood[J].Trends Immunol201435(9):436-442.DOI:10.1016/j.it.2014.06.002.
[7]
Rodriguez SAlizadeh MLamaison C,et al.Follicular lymphoma regulatory T-cell origin and function[J].Front Immunol2024(15):1391404.DOI:10.3389/fimmu.2024.1391404.
[8]
Ding BB, Bi E, Chen H, et al. IL-21 and CD40L synergistically promote plasma cell differentiation through upregulation of Blimp-1 in human B cells[J].J Immunol2013190(4):1827-1836.DOI:10.4049/jimmunol.1201678.
[9]
Shi JHou SFang Q,et al.PD-1 controls follicular T helper cell positioning and function[J].Immunity201849(2):264-274.e4.DOI:10.1016/j.immuni.2018.06.012.
[10]
Wu HDeng YZhao M,et al.Molecular control of follicular helper T cell development and differentiation[J].Front Immunol2018(9):2470.DOI:10.3389/fimmu.2018.02470.
[11]
Chiba S, Sakata-Yanagimoto M. Advances in understanding of angioimmunoblastic T-cell lymphoma[J].Leukemia202034(10):2592-2606.DOI:10.1038/s41375-020-0990-y.
[12]
Fujisawa MSakata-Yanagimoto MNishizawa S,et al.Activation of RHOA-VAV1 signaling in angioimmunoblastic T-cell lymphoma[J].Leukemia201832(3):694-702.DOI:10.1038/leu.2017.273.
[13]
Ng SY, Brown L, Stevenson K, et al. RhoA G17V is sufficient to induce autoimmunity and promotes T-cell lymphomagenesis in mice[J].Blood2018132(9):935-947.DOI:10.1182/blood-2017-11-818617.
[14]
Jacobsen E.Follicular lymphoma:2023 update on diagnosis and management[J].Am J Hematol202297(12):1638-1651.DOI:10.1002/ajh.26737.
[15]
Laurent CDietrich STarte K.Cell cross talk within lymphoma tumor microenvironment:follicular lymphoma as a Paradigm [J].Blood2024143(12):1080-1090.DOI:10.1182/blood.2023021000.
[16]
El Daker SQualls DDerkach A,et al.Deep immunophenotypic dissection and clinical impact of T cells in the follicular lymphoma microenvironment[J].Haematologica2025110(8):1808-1821.DOI:10.3324/haematol.2024.286383.
[17]
Haebe SShree TSathe A,et al.Single-cell analysis can define distinct evolution of tumor sites in follicular lymphoma[J].Blood2021137(21):2869-2880.DOI:10.1182/blood.2020009855.
[18]
Fanale MAssouline SKuruvilla J,et al.Phase IA/II,multicentre,open-label study of the CD40 antagonistic monoclonal antibody lucatumumab in adult patients with advanced non-Hodgkin or Hodgkin lymphoma[J].Br J Haematol2014164(2):258-265.DOI:10.1111/bjh.12630.
[19]
Pangault CAmé-Thomas PRuminy P,et al.Follicular Lymphoma cell niche:identification of a preeminent IL-4-dependent T(FH)-B cell axis [J].Leukemia201024(12):2080-2089.DOI:10.1038/leu.2010.223.
[20]
Mentz MKeay WStrobl CD,et al.PARP14 is a novel target in STAT6 mutant follicular lymphoma[J].Leukemia202236(9):2281-2292.DOI:10.1038/s41375-022-01641-x.
[21]
Mintz MACyster JG.T follicular helper cells in germinal center B cell selection and lymphomagenesis[J].Immunol Rev2020296(1):48-61.DOI:10.1111/imr.12860.
[22]
Cha ZGuo HTu X,et al.Alterations of circulating follicular helper T cells and interleukin 21 in diffuse large B-cell lymphoma[J].Tumour Biol201435(8):7541-7546.DOI:10.1007/s13277-014-1999-5.
[23]
Ma XZha JHe J,et al.T follicular helper cell-mediated IL-21 production suppresses FOXP3 expression of T follicular regulatory-like cells in diffuse large B cell lymphoma patients[J].Hum Immunol202081(8):452-459.DOI:10.1016/j.humimm.2020.05.008.
[24]
Cha ZQian GZang Y,et al.Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway[J].Exp Cell Res2017350(1):154-160.DOI:10.1016/j.yexcr.2016.11.017.
[25]
Wen JNie XZhou Q,et al.Elevated serum IL-10/IL-6 ratio as a novel biomarker for secondary central nervous system lymphoma and poor prognosis in DLBCL[J].Front Immunol2025(16):1656044.DOI:10.3389/fimmu.2025.1656044.
[26]
Mintz MAFelce JHChou MY,et al. The HVEM-BTLA axis restrains T cell help to germinal center B cells and functions as a cell-extrinsic suppressor in lymphomagenesis[J].Immunity201951(2):310-323.e7.DOI:10.1016/j.immuni.2019.05.022.
[27]
Manso BA, Wenzl K, Asmann YW, et al. Whole-exome analysis reveals novel somatic genomic alterations associated with cell of origin in diffuse large B-cell lymphoma[J].Blood Cancer J20177(4):e553.DOI:10.1038/bcj.2017.33.
[28]
de Weerdt IHofland Tde Boer R,et al.Distinct immune composition in lymph node and peripheral blood of CLL patients is reshaped during venetoclax treatment[J].Blood Adv20193(17):2642-2652.DOI:10.1182/bloodadvances.2019000360.
[29]
Wu XFajardo-Despaigne JEZhang C,et al.Altered T follicular helper cell subsets and function in chronic lymphocytic leukemia[J].Front Oncol2021(11):674492.DOI:10.3389/fonc.2021.674492.
[30]
Le Saos-Patrinos C, Loizon S, Zouine A, et al. Elevated levels of circulatory follicular T helper cells in chronic lymphocytic leukemia contribute to B cell expansion[J].J Leukoc Biol2023113(3):305-314.DOI:10.1093/jleuko/qiad006.
[31]
Cha ZZang YGuo H,et al.Association of peripheral CD4+ CXCR5+ T cells with chronic lymphocytic leukemia[J].Tumour Biol201334(6):3579-3585.DOI:10.1007/s13277-013-0937-2.
[32]
Bürkle ANiedermeier MSchmitt-Gräff A,et al.Overexpression of the CXCR5 chemokine receptor,and its ligand,CXCL13 in B-cell chronic lymphocytic leukemia[J].Blood2007110(9):3316-3325.DOI:10.1182/blood-2007-05-089409.
[33]
Heinig KGätjen MGrau M,et al.Access to follicular dendritic cells is a pivotal step in murine chronic lymphocytic leukemia B-cell activation and proliferation[J].Cancer Discov20144(12):1448-1465.DOI:10.1158/2159-8290.CD-14-0096.
[34]
Zhang RGuo SQu J.Exploring the prognostic value of T follicular helper cell levels in chronic lymphocytic leukemia[J].Sci Rep202414(1):22443.DOI:10.1038/s41598-024-73325-8.
[35]
Yano M, Sharpe C, Lance JR, et al. Evaluation of allogeneic and autologous membrane-bound IL-21-expanded NK cells for chronic lymphocytic leukemia therapy[J].Blood Adv20226(20):5641-5654.DOI:10.1182/bloodadvances.2021005883.
[36]
Bunse M, Pfeilschifter J, Bluhm J, et al. CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin's lymphoma and tumor-supportive follicular T helper cells[J].Nat Commun202112(1):240.DOI:10.1038/s41467-020-20488-3.
[37]
Abdel-Rahman SA, Świderek K, Gabr MT. First-in-class small molecule inhibitors of ICOS/ICOSL interaction as a novel class of immunomodulators[J].RSC Med Chem202314(9):1767-1777.DOI:10.1039/d3md00150d.
[38]
Boice MSalloum DMourcin F,et al.Loss of the HVEM tumor suppressor in lymphoma and restoration by modified CAR-T dells[J].Cell2016167(2):405-418.e13.DOI:10.1016/j.cell.2016.08.032.
[39]
Li CZhang LJin Q,et al.Role and application of chemokine CXCL13 in central nervous system lymphoma[J].Ann Hematol2024103(8):2671-2680.DOI:10.1007/s00277-023-05560-4.
[1] 李雨秋, 莫红楠. 乳腺癌肿瘤微环境特征及免疫治疗新进展[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(06): 331-338.
[2] 王思竣, 王琼, 李珂雨, 袁新普, 张硕珉, 马睿, 谢天宇, 张朝军. 胃上部癌新辅助化疗联合免疫治疗后实施近端胃切除术的临床疗效分析[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(06): 637-641.
[3] 钱龙, 蔡大明, 王行舟, 艾世超, 胡琼源, 孙锋, 宋鹏, 王峰, 王萌, 陆晓峰, 朱欢欢, 沈晓菲, 管文贤. 局部不可切除胃癌转化治疗(联合免疫治疗)后淋巴结转移的相关危险因素分析[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(06): 624-627.
[4] 高峰, 郝少龙, 孙浩, 韩威. 三级淋巴结构在胰腺癌中的研究进展[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(05): 570-573.
[5] 廖志成, 朱黎, 曾志宇. 广东省医学会泌尿外科疑难病例多学科会诊(第27期)——晚期肾癌[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2025, 19(05): 669-676.
[6] 李才坤, 张又红, 肖斌彬, 温盼, 刘醒, 刘志栋, 周剑辉, 温春玲, 叶劲, 严恒琛. 三维斑点追踪在肺癌患者免疫治疗后左心房功能损害评价的应用[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(05): 821-823.
[7] 徐蓓, 厉小梅, 王俐, 李雨薇, 徐晓玲, 陈卓. 原发性干燥综合征伴肺结节的临床特征[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(05): 673-678.
[8] 骆鑫源, 王元昕, 周远畅, 陈可蕙, 李泽歆, 张基旺, 张磊升, 郑朝晖. 纳米材料在增强自然杀伤细胞靶向治疗中的应用研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2025, 15(05): 312-320.
[9] 张宇涵, 吴添庆, 高汶卿, 郑梽楷, 贺珉睿, 周仲国. 不可切除性肝内胆管癌不同治疗方式疗效和安全性的Meta分析[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(06): 939-947.
[10] 许侨东, 马志延, 冯庚壬, 钟海彬, 刘坚锐, 古松钢. 肝肺多发性原发性癌转化治疗后行腹腔镜肝右前叶切除术一例(附视频)[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(06): 973-976.
[11] 胡铭语, 李敬东, 肖雨竹, 黄杰. 初始不可切除肝癌患者转化治疗序贯手术的临床疗效分析[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(05): 754-760.
[12] 赵南, 张明凯, Bhargava Divija, 赵世光, 张大明. 结直肠癌脑转移的临床特征与治疗策略进展[J/OL]. 中华结直肠疾病电子杂志, 2025, 14(05): 427-435.
[13] 王春茂, 韩鸣, 王子彤. 局限期小细胞肺癌新辅助治疗后完全病理学缓解五例[J/OL]. 中华临床医师杂志(电子版), 2025, 19(07): 550-554.
[14] 侯雨函, 姜福金, 王苏贵. 膀胱癌免疫治疗的研究进展[J/OL]. 中华临床医师杂志(电子版), 2025, 19(06): 471-475.
[15] 武世伦, 姚常玉, 许力, 狄治杉, 夏奇, 孙文兵, 孔健. 肿瘤相关巨噬细胞在肝细胞癌血管新生中的作用及研究进展[J/OL]. 中华临床医师杂志(电子版), 2025, 19(05): 388-391.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?