# Dysregulation of the Hippo pathway enhances PD-L2 transcription to promote immune evasion in head and neck squamous cell carcinoma

Article · Ando T, Okamoto K, Sato K, Goto Y, Izumi H, Kataoka N, Ueda Y, Kobayashi Y, Omachi K, Maeda Y, Furusho H, Iglesias-Bartolome R, Yoshimoto T, Shintani T, Yanamoto S, Miyauchi M, Gutkind JS, Kajiya M

- Archive id: doi:10.1038/s42003-026-11092-0
- Published: 2026-10-23
- Venue: Communications biology
- DOI: https://doi.org/10.1038/s42003-026-11092-0
- PMID: 42919899
- PMCID: PMC13694708
- Citations: 0
- Source URL: https://doi.org/10.1038/s42003-026-11092-0
- PDF: https://europepmc.org/articles/PMC13694708/pdf
- Provenance: europepmc

## Abstract

The Hippo pathway and its downstream effectors, YAP/TAZ, exhibit aberrant regulation in head and neck squamous cell carcinoma, facilitating cancer cell growth. However, the influence of YAP/TAZ on cancer immune evasion remains poorly understood. Herein, we show that cancer patients harboring mutations regulating the Hippo pathway and YAP/TAZ hyperactivation may be sensitized to immune checkpoint inhibitor (ICI) therapy owing to genome instability and PD-L2 expression. LATS1/2 deletion, accompanied by YAP/TAZ hyperactivation, was associated with loss of squamous differentiation and genome instability, which may contribute to elevated DNA damage. Our data suggest that YAP/TAZ may recruit TEAD, BRD4, and RNA polymerase Ⅱ to the super-enhancer and promoter regions of PD-L1 and PD-L2. YAP/TAZ predominantly contribute to PD-L2 expression, which is associated with Stat3 activation, partially enhancing PD-L1 transcription. YAP/TAZ-activated cells can be targeted by antigen-specific T cells but evade them through PD-L2. These findings suggest that Hippo pathway alterations and associated YAP/TAZ hyperactivation may serve as potential prognostic factors for stratifying patients undergoing ICI therapy. Targeting YAP/TAZ/TEAD could offer a promising treatment avenue for cancers harboring YAP/TAZ hyperactivation.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Cancer Immunotherapy](https://space-kitty.com/topics/cancer-immunotherapy)

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