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

Wu, Jizhun, Zhang, Lu, Zhao, Zihan, Liu, Yuping, Li, Zhengxing, Feng, Xiaohang, Zhang, Lin, Yao, Xiang, Du, Jun, Chen, Liang, Zhou, Zhuolong·2025·Ageing Research Reviews
DOI 10.1016/j.arr.2025.102783
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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 an…

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Metadata

Authors
Wu, J., Zhang, L., Zhao, Z., Liu, Y., Li, Z., Feng, X., Zhang, L., Yao, X., Du, J., Chen, L., & Zhou, Z.
Venue
Ageing Research Reviews
Publisher
Elsevier BV
Published
2025-07
Volume
109
Pages
102783
ISSN
1568-1637
DOI
10.1016/j.arr.2025.102783
Cited by
10
References
48
Language
en
Licence
Funders
  • Natural Science Foundation of Shenzhen Municipality (JCYJ20241202124303005)
  • University of Edinburgh
  • Zhejiang Province Natural Science Foundation (LHDMZ25H160001)

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