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FAK scaffolds immune escape in pancreatic cancer
  1. Adrian Blanco-Gomez,
  2. Claus Jorgensen
  1. Systems Oncology, Cancer Research UK Manchester Institute, Manchester, UK
  1. Correspondence to Dr Claus Jorgensen, Cancer Research UK Manchester Institute, Manchester, M20 4BX, UK; Claus.Jorgensen{at}

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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).

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, …

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  • Contributors AB-G conceived and wrote the commentary and made the figure. CJ conceived and cowrote the commentary.

  • Funding Work in systems oncology is supported by a Cancer Research UK Institute Award (C5759/A27412), a Cancer Research UK Programme Award (C13329/A21671) and a European Research Council Consolidator Award (ERC-2017-CoG 772577).

  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.

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