2. Academic Validation
  3. Charged substrate treatment enhances T cell mediated cancer immunotherapy

Charged substrate treatment enhances T cell mediated cancer immunotherapy

  • Nat Commun. 2025 Feb 12;16(1):1585. doi: 10.1038/s41467-025-56858-y.
Jia Song # 1 2 3,  Yanhui Lu # 1 3,  Lulu Liu # 2 3,  Xiaoyu Han 2 3,  Yanhong Meng 4,  Boon Chin Heng 1 3,  Xin Zhang 5,  Qun Cui 1 3,  Ziqi Liu 1 3,  Yusi Guo 2 3,  Xiaona Zheng 1 3,  Fuping You 5,  Dan Lu 6,  Xuehui Zhang 7 8 9,  Xuliang Deng 10 11
Affiliations

Affiliations

  • 1 Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, PR China.
  • 2 Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, PR China.
  • 3 National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials & Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, PR China.
  • 4 Department of Clinical Laboratory, Peking University School and Hospital of Stomatology, Beijing, PR China.
  • 5 Institute of Systems Biomedicine, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, PR China.
  • 6 Institute of Systems Biomedicine, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, PR China. taotao@bjmu.edu.cn.
  • 7 Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, PR China. zhangxuehui@bjmu.edu.cn.
  • 8 National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials & Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, PR China. zhangxuehui@bjmu.edu.cn.
  • 9 Oral Translational Medicine Research Center, Joint Training base for Shanxi Provincial Key Laboratory in Oral and Maxillofacial Repair, Reconstruction and Regeneration, The First People's Hospital of Jinzhong, Jinzhong, Shanxi Province, PR China. zhangxuehui@bjmu.edu.cn.
  • 10 Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, PR China. kqdengxuliang@bjmu.edu.cn.
  • 11 National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials & Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, PR China. kqdengxuliang@bjmu.edu.cn.
  • # Contributed equally.
PMID: 39939595 DOI: 10.1038/s41467-025-56858-y
Abstract

Biophysical cues play a crucial role in T Cell Biology, yet their implications in adoptive T cell therapy (ACT) remain largely unknown. Here, we investigate the effect of electrical stimuli on CD8+ T cells using a charged substrate composed of electroactive nanocomposites with tunable surface charge intensities. Electrical stimuli enhance the persistence and tumor-suppressive efficacy of transferred T cells, with effects dependent on substrate charge. Single-cell RNA-sequencing analysis unveils a decrease in virtual memory T (Tvm) cells and an increase in proliferative potential T (Tpp) cells, which exhibit superior antitumor activity and metabolic adaptations relative to those treated with uncharged substrate. ATAC-seq profiling demonstrates heightened accessibility at upstream binding sites for EGR1, a transcription factor critical for Tpp cell differentiation. Mechanistically, the charged substrate disrupts ionic TCR-lipid interactions, amplifies TCR signaling, and activates EGR1, thereby impeding Tvm polarization during ex vivo culture. Our findings thus highlight the importance of extracellular electrical stimuli in shaping T cell fate, offering potential for optimizing ACT for therapeutic applications.

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