PIEZO1 mechanically regulates the antitumour cytotoxicity of T lymphocytes.
Ruiyang PangWeihao SunYingyun YangDahan WenFeng LinDingding WangKailong LiNing ZhangJunbo LiangChunyang XiongYuying LiuPublished in: Nature biomedical engineering (2024)
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.
Keyphrases
- induced apoptosis
- high fat diet induced
- transcription factor
- gene expression
- signaling pathway
- cell proliferation
- cancer therapy
- type diabetes
- adipose tissue
- squamous cell carcinoma
- metabolic syndrome
- insulin resistance
- endoplasmic reticulum stress
- long non coding rna
- skeletal muscle
- cell death
- heat shock
- fluorescent probe