Suppression of non-muscle myosin II boosts T cell cytotoxicity against tumors.

Increasing evidence highlights the importance of immune mechanoregulation in establishing and sustaining tumor-specific cytotoxicity required for desirable immunotherapeutic outcomes. However, the molecular connections between mechanobiological inputs and outputs and the designated immune activities remain largely unclear. Here, we show that partial inhibition of non-muscle myosin II (NM II) augmented the traction force exerted by T cells and potentiated T cell cytotoxicity against tumors.

PIEZO1 mechanically regulates the antitumour cytotoxicity of T lymphocytes.

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.