2. Academic Validation
  3. A chimeric peptide promotes immune surveillance of senescent cells in injury, fibrosis, tumorigenesis and aging

A chimeric peptide promotes immune surveillance of senescent cells in injury, fibrosis, tumorigenesis and aging

  • Nat Aging. 2025 Jan;5(1):28-47. doi: 10.1038/s43587-024-00750-9.
Xinliang Ming # 1 2 3,  Ze Yang # 1 2,  Yuqiao Huang # 1 2,  Zhiguo Wang 4,  Qingyan Zhang 1 2,  Changchang Lu 1 2,  Yandi Sun 1 2,  Yuanhao Chen 1 2,  Liang Zhang 5,  Jicheng Wu 1 2 6,  Hao Shou 1 2,  Zhimin Lu 2 7 8 9 10,  Ben Wang 11 12 13 14 15 16
Affiliations

Affiliations

  • 1 Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 2 Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
  • 3 Department of Clinical Laboratory, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 4 Institute of Ageing Research, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, China.
  • 5 Center for Molecular Diagnosis and Precision Medicine, Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 6 Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.
  • 7 Institute of Fundamental and Transdisciplinary Research, Zhejiang University, Hangzhou, China.
  • 8 Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Hangzhou, China.
  • 9 Cancer Center, Zhejiang University, Hangzhou, China.
  • 10 Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 11 Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. benwang@zju.edu.cn.
  • 12 Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China. benwang@zju.edu.cn.
  • 13 Institute of Fundamental and Transdisciplinary Research, Zhejiang University, Hangzhou, China. benwang@zju.edu.cn.
  • 14 Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Hangzhou, China. benwang@zju.edu.cn.
  • 15 Cancer Center, Zhejiang University, Hangzhou, China. benwang@zju.edu.cn.
  • 16 State Key Laboratory of Transvascular Implantation Devices, Hangzhou, China. benwang@zju.edu.cn.
  • # Contributed equally.
PMID: 39623223 DOI: 10.1038/s43587-024-00750-9
Abstract

The accumulation of senescent cells can lead to tissue degeneration, chronic inflammatory disease and age-related tumorigenesis. Interventions such as senolytics are currently limited by off-target toxicity, which could be circumvented by instead enhancing immune-mediated senescent cell clearance; however, immune surveillance of senescent cells is often impeded by immunosuppressive factors in the inflammatory microenvironment. Here, we employ a chimeric peptide as a 'matchmaker' to bind to the urokinase-type plasminogen activator receptor, a cell surface marker of senescent cells. This peptide modifies the cell surface with polyglutamic acid, promoting immune cell-mediated responses through glutamate recognition. By enhancing the recruitment of immune cells and directly coupling senescent cells and immune cells, we show that this chimeric peptide induces immune clearance of senescent cells and restores tissue homeostasis in conditions such as liver fibrosis, lung injury, Cancer and natural aging in mice. This chimeric peptide introduces an immunological conversion strategy that rebalances the senescent immune microenvironment, offering a promising direction for aging immunotherapy.

Figures
Products