PIEZO1 mechanically regulates the antitumour cytotoxicity of T lymphocytes

Ruiyang Pang; Weihao Sun; Yingyun Yang; Dahan Wen; Feng Lin; Dingding Wang; Kailong Li; Ning Zhang; Junbo Liang; Chunyang Xiong; Yuying Liu

doi:10.1038/s41551-024-01188-5

PIEZO1 mechanically regulates the antitumour cytotoxicity of T lymphocytes

Ruiyang Pang, Weihao Sun, Yingyun Yang, Dahan Wen, Feng Lin, Dingding Wang, Kailong Li, Ning Zhang, Junbo Liang (Lead / Corresponding author), Chunyang Xiong (Lead / Corresponding author), Yuying Liu (Lead / Corresponding author)

MRC PPU

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Nature Biomedical Engineering
Early online date	21 Mar 2024
DOIs	https://doi.org/10.1038/s41551-024-01188-5
Publication status	E-pub ahead of print - 21 Mar 2024

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41551-024-01188-5

Cite this

@article{a4b78ee0dbe5484aa21c06e0b21a64c7,

title = "PIEZO1 mechanically regulates the antitumour cytotoxicity of T lymphocytes",

abstract = "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.",

author = "Ruiyang Pang and Weihao Sun and Yingyun Yang and Dahan Wen and Feng Lin and Dingding Wang and Kailong Li and Ning Zhang and Junbo Liang and Chunyang Xiong and Yuying Liu",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature Limited 2024.",

year = "2024",

month = mar,

day = "21",

doi = "10.1038/s41551-024-01188-5",

language = "English",

journal = "Nature Biomedical Engineering",

issn = "2157-846X",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - PIEZO1 mechanically regulates the antitumour cytotoxicity of T lymphocytes

AU - Pang, Ruiyang

AU - Sun, Weihao

AU - Yang, Yingyun

AU - Wen, Dahan

AU - Lin, Feng

AU - Wang, Dingding

AU - Li, Kailong

AU - Zhang, Ning

AU - Liang, Junbo

AU - Xiong, Chunyang

AU - Liu, Yuying

PY - 2024/3/21

Y1 - 2024/3/21

N2 - 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.

AB - 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.

U2 - 10.1038/s41551-024-01188-5

DO - 10.1038/s41551-024-01188-5

M3 - Article

C2 - 38514773

SN - 2157-846X

JO - Nature Biomedical Engineering

JF - Nature Biomedical Engineering

ER -

PIEZO1 mechanically regulates the antitumour cytotoxicity of T lymphocytes

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this