Mechanosensitive YAP-RUNX1 signaling drives T(H)1 cell dysfunction and tumor immunosuppression.

Elevated tissue stiffness in pancreatic cancer subverts tumor-infiltrating TH1 cells into a dysfunction program, linked to immunosuppression, via YAP nuclear activation and RUNX1 cooperation.

• Why it matters: Tumor stiffening is common, but how it specifically reprograms TH1 cells to promote immunosuppression in the tumor microenvironment is not well defined.
• What they did: The study used stiffness-driven mechanotransduction through integrins to activate YAP, then assessed YAP nuclear translocation and YAP–RUNX1 transcriptional upregulation of dysfunction-associated genes.
• The result: Blocking YAP expression or disrupting YAP–RUNX1 interaction reverses TH1 dysfunction, restores antitumor immunity, and suggests a therapeutic route for stiff tumors.

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