中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 42 Issue 8
Aug.  2026
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2026  >  42(8): 1980-1984

Mechanism of action of T cell senescence in the progression of liver fibrosis to liver cirrhosis in elderly patients with chronic hepatitis B

DOI: 10.12449/JCH260835

  • Department of General Practice，Ganmei Hospital Affiliated to Kunming Medical University，Kunming 650224，China

Research funding:

Yunnan Province Science and Technology Department-Basic Research Program (202401AY070001-309);

Yunnan Province Science and Technology Department-Basic Research Program (202601AT070201);

Kunming Municipal Health Commission Scientific Research Project (2025-02-07-001)

More Information
  • Corresponding author: Xu Xu， xuxu@kmmu.edu.cn （ORCID： 0009-0005-1492-4364）
  • Received Date: 2026-01-05
  • Accepted Date: 2026-03-09
  • Published Date: 2026-08-25
    Abstract
  • Liver fibrosis is a key pathological process in the transition from chronic liver disease to cirrhosis， especially in elderly patients with chronic hepatitis B， and this process is characterized by rapid progression and poor prognosis. T cell function gradually declines with aging， and T cell senescence is recognized as a key immunological mechanism accelerating the progression of liver fibrosis. Current studies have shown that senescent T cells promote the transition from liver fibrosis to liver cirrhosis by altering the liver inflammatory microenvironment， modulating the activity of fibrosis-related cells， and impairing immune surveillance function. This article systematically reviews the molecular mechanisms of T cell senescence and its role in the progression of liver fibrosis in elderly patients with chronic hepatitis B， as well as novel therapeutic approaches targeting immunosenescence with reference to the latest immunological findings and stem cell-based therapeutic strategies， so as to provide theoretical support for precise intervention for such patients.

     

    • FullText(HTML)
  • loading
    • References(41)
  • [1]
    Jia Y H, Ma L Y, Wang Y D, et al. NLRP3 inflammasome and related cytokines reflect the immune status of patients with HBV-ACLF[J]. Mol Immunol, 2020, 120: 179- 186. DOI: 10.1016/j.molimm.2020.01.011.
    [2]
    Zecca A, Barili V, Canetti D, et al. Energy metabolism and cell motility defect in NK-cells from patients with hepatocellular carcinoma[J]. Cancer Immunol Immunother, 2020, 69( 8): 1589- 1603. DOI: 10.1007/s00262-020-02561-4.
    [3]
    Chen Q B, Lai L M, Chi X L, et al. CD19+CD24hiCD38hi B cell dysfunction in primary biliary cholangitis[J]. Mediators Inflamm, 2020, 2020: 3019378. DOI: 10.1155/2020/3019378.
    [4]
    Yang X X, Li J W, Ren M L, et al. Comprehensive analysis of immune signatures in primary biliary cholangitis and autoimmune hepatitis[J]. J Leukoc Biol, 2024, 117( 1): qiae085. DOI: 10.1093/jleuko/qiae085.
    [5]
    Li B, Xiong W Y, Zuo W, et al. Proximal telomeric decompaction due to telomere shortening drives FOXC1-dependent myocardial senescence[J]. Nucleic Acids Res, 2024, 52( 11): 6269- 6284. DOI: 10.1093/nar/gkae274.
    [6]
    Wang M, Guo Z, Zhao S S, et al. CD49d promotes T-cell senescence in chronic lymphocytic leukaemia[J]. Br J Haematol, 2025, 207( 1): 80- 91. DOI: 10.1111/bjh.20135.
    [7]
    Pangrazzi L, Weinberger B. T cells, aging and senescence[J]. Exp Gerontol, 2020, 134: 110887. DOI: 10.1016/j.exger.2020.110887.
    [8]
    Slaets H, Veeningen N, de Keizer P L J, et al. Are immunosenescent T cells really senescent[J]. Aging Cell, 2024, 23( 10): e14300. DOI: 10.1111/acel.14300.
    [9]
    Kasamatsu T. Implications of senescent T cells for cancer immunotherapy[J]. Cancers, 2023, 15( 24): 5835. DOI: 10.3390/cancers15245835.
    [10]
    Nakagami H. Cellular senescence and senescence-associated T cells as a potential therapeutic target[J]. Geriatr Gerontol Int, 2020, 20( 2): 97- 100. DOI: 10.1111/ggi.13851.
    [11]
    Nga H T, Nguyen T L, Yi H S. T-cell senescence in human metabolic diseases[J]. Diabetes Metab J, 2024, 48( 5): 864- 881. DOI: 10.4093/dmj.2024.0140.
    [12]
    Laphanuwat P, Gomes D C O, Akbar A N. Senescent T cells: Beneficial and detrimental roles[J]. Immunol Rev, 2023, 316( 1): 160- 175. DOI: 10.1111/imr.13206.
    [13]
    Huang L, Zhang C G, Jiang A M, et al. T-cell senescence in the tumor microenvironment[J]. Cancer Immunol Res, 2025, 13( 5): 618- 632. DOI: 10.1158/2326-6066.CIR-24-0894.
    [14]
    Mathiasen S L, Gall-Mas L, Pateras I S, et al. Bacterial genotoxins induce T cell senescence[J]. Cell Rep, 2021, 35( 10): 109220. DOI: 10.1016/j.celrep.2021.109220.
    [15]
    Fukushima Y, Ueno R, Minato N, et al. Senescence-associated T cells in immunosenescence and diseases[J]. Int Immunol, 2025, 37( 3): 143- 152. DOI: 10.1093/intimm/dxae056.
    [16]
    Covre L P, de Maeyer R P H, Gomes D C O, et al. The role of senescent T cells in immunopathology[J]. Aging Cell, 2020, 19( 12): e13272. DOI: 10.1111/acel.13272.
    [17]
    Yi H S, Kim S Y, Kim J T, et al. T-cell senescence contributes to abnormal glucose homeostasis in humans and mice[J]. Cell Death Dis, 2019, 10( 3): 249. DOI: 10.1038/s41419-019-1494-4.
    [18]
    Sim B C, Kang Y E, You S K, et al. Hepatic T-cell senescence and exhaustion are implicated in the progression of fatty liver disease in patients with type 2 diabetes and mouse model with nonalcoholic steatohepatitis[J]. Cell Death Dis, 2023, 14( 9): 618. DOI: 10.1038/s41419-023-06146-8.
    [19]
    Shive C L, Kowal C M, Desotelle A F, et al. Endotoxemia associated with liver disease correlates with systemic inflammation and T cell exhaustion in hepatitis C virus infection[J]. Cells, 2023, 12( 16): 2034. DOI: 10.3390/cells12162034.
    [20]
    Zhang H Y, Wang X C, Zhang X, et al. Hepatic ferroptosis induced by Clonorchis sinensis exacerbates liver fibrosis[J]. PLoS Negl Trop Dis, 2025, 19( 6): e0013164. DOI: 10.1371/journal.pntd.0013164.
    [21]
    Yashaswini C N, Qin T Y, Bhattacharya D, et al. Phenotypes and ontogeny of senescent hepatic stellate cells in metabolic dysfunction-associated steatohepatitis[J]. J Hepatol, 2024, 81( 2): 207- 217. DOI: 10.1016/j.jhep.2024.03.014.
    [22]
    Ezhilarasan D. Hepatic stellate cells in the injured liver: Perspectives beyond hepatic fibrosis[J]. J Cell Physiol, 2022, 237( 1): 436- 449. DOI: 10.1002/jcp.30582.
    [23]
    Shrivastava S, Kottilil S, Sherman K E, et al. CCR5+ T-cells homed to the liver exhibit inflammatory and profibrogenic signatures in chronic HIV/HCV-coinfected patients[J]. Viruses, 2021, 13( 10): 2074. DOI: 10.3390/v13102074.
    [24]
    Wu J Z, Zhang L, Zhao Z H, et al. Advancing T-cell immunotherapy for cellular senescence and disease: Mechanisms, challenges, and clinical prospects[J]. Ageing Res Rev, 2025, 109: 102783. DOI: 10.1016/j.arr.2025.102783.
    [25]
    Chai J Q, Li L Y, Wu Q M, et al. CD96: Immunoregulation and its role and prospect in immunotherapy of primary hepatocellular carcinoma[J]. Eur J Gastroenterol Hepatol, 2025, 37( 5): 534- 539. DOI: 10.1097/MEG.0000000000002916.
    [26]
    Zhang Q S, Wang J N, Yang T L, et al. SHMT2 regulates CD8+ T cell senescence via the reactive oxygen species axis in HIV-1 infected patients on antiretroviral therapy[J]. eBioMedicine, 2025, 112: 105533. DOI: 10.1016/j.ebiom.2024.105533.
    [27]
    Turano P S, Akbulut E, Dewald H K, et al. Epigenetic mechanisms regulating CD8+ T cell senescence in aging humans[J]. bioRxiv, 2025. DOI: 10.1101/2025.01.17.633634.[ Epub ahead of print]
    [28]
    Wang S, Wang X O, Zheng X Y, et al. NGR-modified curcumin nanovesicles reverse immunotherapy resistance in triple-negative breast cancer via TLR9 and mTOR pathway modulation[J]. Cell Biol Toxicol, 2025, 41( 1): 109. DOI: 10.1007/s10565-025-10055-1.
    [29]
    Admasu T D, Yu J S. Harnessing immune rejuvenation: Advances in overcoming T cell senescence and exhaustion in cancer immunotherapy[J]. Aging Cell, 2025, 24( 5): e70055. DOI: 10.1111/acel.70055.
    [30]
    Khosla S, Farr J N, Tchkonia T, et al. The role of cellular senescence in ageing and endocrine disease[J]. Nat Rev Endocrinol, 2020, 16( 5): 263- 275. DOI: 10.1038/s41574-020-0335-y.
    [31]
    Nazarie Ignat S R, Gharbia S, Hermenean A, et al. Regenerative potential of mesenchymal stem cells’(MSCs) secretome for liver fibrosis therapies[J]. Int J Mol Sci, 2021, 22( 24): 13292. DOI: 10.3390/ijms222413292.
    [32]
    Bozorgi V, Babaahmadi M, Salehi M, et al. From signaling pathways to clinical trials: Mesenchymal stem cells as multimodal regenerative architects in liver cirrhosis therapy[J]. Stem Cell Res Ther, 2025, 16( 1): 421. DOI: 10.1186/s13287-025-04535-8.
    [33]
    Janelle V, Delisle J S. T-cell dysfunction as a limitation of adoptive immunotherapy: Current concepts and mitigation strategies[J]. Cancers, 2021, 13( 4): 598. DOI: 10.3390/cancers13040598.
    [34]
    Calviño C, Ceballos C, Alfonso A, et al. Optimization of universal allogeneic CAR-T cells combining CRISPR and transposon-based technologies for treatment of acute myeloid leukemia[J]. Front Immunol, 2023, 14: 1270843. DOI: 10.3389/fimmu.2023.1270843.
    [35]
    Liu Q W, Li J F, Sun X Q, et al. Immunosenescence and cancer: Molecular hallmarks, tumor microenvironment remodeling, and age-specific immunotherapy challenges[J]. J Hematol Oncol, 2025, 18( 1): 81. DOI: 10.1186/s13045-025-01735-w.
    [36]
    Li Y K, Yi J S, Howard J F, et al. Cellular changes in eculizumab early responders with generalized myasthenia gravis[J]. Clin Immunol, 2021, 231: 108830. DOI: 10.1016/j.clim.2021.108830.
    [37]
    Takasugi M, Yoshida Y, Ohtani N. Cellular senescence and the tumour microenvironment[J]. Mol Oncol, 2022, 16( 18): 3333- 3351. DOI: 10.1002/1878-0261.13268.
    [38]
    Wang X D, Wang J, Peng H D, et al. Role of immune cell interactions in alcohol-associated liver diseases[J]. Liver Res, 2024, 8( 2): 72- 82. DOI: 10.1016/j.livres.2024.06.002.
    [39]
    Zeng W F, Liu F R, Liu Y C, et al. Targeting TM4SF1 promotes tumor senescence enhancing CD8+ T cell cytotoxic function in hepatocellular carcinoma[J]. Clin Mol Hepatol, 2025, 31( 2): 489- 508. DOI: 10.3350/cmh.2024.0934.
    [40]
    Sakai Y, Fukunishi S, Takamura M, et al. Clinical trial of autologous adipose tissue-derived regenerative(stem) cells therapy for exploration of its safety and efficacy[J]. Regen Ther, 2021, 18: 97- 101. DOI: 10.1016/j.reth.2021.04.003.
    [41]
    Sakai Y, Fukunishi S, Takamura M, et al. Regenerative therapy for liver cirrhosis based on intrahepatic arterial infusion of autologous subcutaneous adipose tissue-derived regenerative(stem) cells: Protocol for a confirmatory multicenter uncontrolled clinical trial[J]. JMIR Res Protoc, 2020, 9( 3): e17904. DOI: 10.2196/17904.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(1)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (7) PDF downloads(0) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return