Mechanotransduction via YAP/TAZ shapes the tumour immune microenvironment

Spatio-temporal heterogeneity within the tumour immune microenvironment (TIME) underpins therapeutic resistance to cancer immunotherapy across solid malignancies, yet the mechanistic drivers governing such heterogeneous immune landscapes remain incompletely defined. Biophysical mechanical cues constitute pervasive microenvironmental regulators that dynamically remodel immune homeostasis throughout tumour initiation, local progression and distal metastatic colonisation. As core mechanotransductive effectors, YAP and TAZ integrate extracellular mechanical inputs into cell-intrinsic transcriptional programmes, functioning as a central molecular nexus bridging physical microenvironment remodelling and TIME specification. Mechanosensory activation of YAP/TAZ remodels the functional phenotypes of malignant epithelial cells, cancer-associated fibroblasts (CAFs) and multiple immune subsets, thereby dictating the spatial distribution, polarisation status and effector competence of tumour-infiltrating immune cells to establish spatially segregated immune-suppressive niches. Fueled by advances in single-cell transcriptomics and spatial multi-omics, recent findings have unravelled YAP/TAZ regulatory circuits that sculpt divergent TIME landscapes in mechanical pathways. Here, we synthesise contemporary progress delineating how YAP/TAZ-dependent mechanotransduction programmes establish TIME spatiotemporal heterogeneity, highlight translational therapeutic strategies centred on perturbing this mechanochemical axis to dismantle mechanical immune suppression, and discuss outstanding challenges to unlock targeted TIME remodelling for overcoming clinical immunotherapy failure in solid tumours.