PIEZO1 mechanically regulates the antitumour cytotoxicity of T lymphocytes.
Journal
Nature biomedical engineering
ISSN: 2157-846X
Titre abrégé: Nat Biomed Eng
Pays: England
ID NLM: 101696896
Informations de publication
Date de publication:
21 Mar 2024
21 Mar 2024
Historique:
received:
27
06
2023
accepted:
05
02
2024
medline:
22
3
2024
pubmed:
22
3
2024
entrez:
22
3
2024
Statut:
aheadofprint
Résumé
The killing function of cytotoxic T cells can be enhanced biochemically. Here we show that blocking the mechanical sensor PIEZO1 in T cells strengthens their traction forces and augments their cytotoxicity against tumour cells. By leveraging cytotoxic T cells collected from tumour models in mice and from patients with cancers, we show that PIEZO1 upregulates the transcriptional factor GRHL3, which in turn induces the expression of the E3 ubiquitin ligase RNF114. RNF114 binds to filamentous actin, causing its downregulation and rearrangement, which depresses traction forces in the T cells. In mice with tumours, the injection of cytotoxic T cells collected from the animals and treated with a PIEZO1 antagonist promoted their infiltration into the tumour and attenuated tumour growth. As an immunomechanical regulator, PIEZO1 could be targeted to enhance the outcomes of cancer immunotherapies.
Identifiants
pubmed: 38514773
doi: 10.1038/s41551-024-01188-5
pii: 10.1038/s41551-024-01188-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82341009, 92169101
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82073184
Organisme : Chinese Academy of Medical Sciences (CAMS)
ID : 2021-I2M-1-066
Organisme : Natural Science Foundation of Beijing Municipality (Beijing Natural Science Foundation)
ID : Z200017
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
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