Advancing T-cell immunotherapy for cellular senescence and disease: Mechanisms, challenges, and clinical prospects.

Journal: Ageing research reviews
Published Date: Jul 1, 2025

Abstract

Cellular senescence is a complex biological process with a dual role in tissue homeostasis and aging-related pathologies. Accumulation of senescent cells promotes chronic inflammation, tissue dysfunction, age-related diseases, and tumor suppression. Recent advancements in immunotherapy have positioned T cell-based approaches as precision tools for the targeted clearance of senescent cells, offering a novel avenue for anti-aging interventions. This review explores the molecular mechanisms underlying cellular senescence, focusing on its immunogenic features and interactions with T cells, including T-cell activation, antigen recognition, modulation of tumor microenvironment (TME), and immune evasion strategies. Innovations such as chimeric antigen receptor (CAR)-T cells, immune checkpoint therapies, and SASP-neutralizing approaches are highlighted as breakthrough strategies for enhancing senescent cell eradication. The integration of multi-omics and artificial intelligence is further catalyzing the development of personalized therapies to amplify immune surveillance and tissue rejuvenation. Clinically, T cell-based interventions hold promise for mitigating age-related pathologies and extending healthspan, yet challenges remain in optimizing target specificity, countering immunosuppressive niches, and overcoming immune senescence in aging populations. This review synthesizes current advances and challenges, highlighting the potential of T cell immunotherapy as a cornerstone of anti-aging medicine and emphasizing the need for interdisciplinary innovation to translate preclinical findings into transformative therapies for aging and age-related diseases.

Authors

  • Jizhun Wu
    Department of Colorectal Surgery, The Second Affiliated Hospital, and Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China.
  • Lu Zhang
    Department of Computer Science and Engineering, The University of Texas at Arlington, Arlington, TX, United States.
  • Zihan Zhao
    Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Institute of Urology, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China.
  • Yuping Liu
    Health Management Center and Physical Examination Center of Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. liuyuping555@126.com.
  • Zhengxing Li
    Electric Power Research Institute, Yunnan Power Grid Co., Ltd., Kunming, Yunnan, China.
  • Xiaohang Feng
    Department of Colorectal Surgery, The Second Affiliated Hospital, and Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China.
  • Lin Zhang
    Laboratory of Molecular Translational Medicine, Centre for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Clinical Research Center for Birth Defects of Sichuan Province, West China Second Hospital, Sichuan University, Chengdu, Sichuan, 610041, China. Electronic address: zhanglin@scu.edu.cn.
  • Xiang Yao
    Department of Colorectal Surgery, The Second Affiliated Hospital, and Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China.
  • Jun Du
    Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, P.R. China.
  • Liang Chen
    Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
  • Zhuolong Zhou
    Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202.

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