Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease in urgent need of improved therapy. A characteristic feature of PDAC is an abundant fibroinflammatory reaction that contributes to the treatment recalcitrancy of this disease. Here, tumour cells coinhabit a stiff, densely remodelled extracellular matrix (ECM) with abundant cancer-associated fibroblasts, immunosuppressive myeloid cell populations and regulatory T-cells that synergise to drive a CD8 T-cell-excluded tumour microenvironment (TME).1 The immune-deserted TME, in combination with a low neoantigen burden, is considered a major reason for the poor response to immune checkpoint inhibitors in PDAC.

While several studies have established that a remodelled ECM drives immune exclusion,2 the link between tissue stiffening and tumour cell autonomous mechanisms of immune evasion is less well explored. In a recent study, Canel and coworkers3 uncover a new mechanistic link between the scaffolding function of focal adhesion kinase (FAK) and PDAC immune escape (figure 1).

Focal adhesion kinase (FAK) nuclear scaffolding function mediates immune escape in pancreatic cancer. In pancreatic ductal adenocarcinoma (PDAC) cells, nuclear FAK stabilises signal transducer and activator of transcription 1 and 3 (STAT1/STAT3) heterodimers thereby inhibiting interferon gamma (IFNγ) responsive genes, including mediators of antigen processing and presentation. In FAK−/− cells, or in cells where FAK cannot translocate to the nucleus, antigen processing and presentation is restored, allowing CD8 T-cells to mount an efficient antitumour response. ECM, …