{"id":"doi:10.1038/s42003-026-11092-0","kind":"article","title":"Dysregulation of the Hippo pathway enhances PD-L2 transcription to promote immune evasion in head and neck squamous cell carcinoma","authors":["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"],"author_count":18,"year":2026,"published":"2026-10-23","venue":"Communications biology","cited_by":0,"doi":"10.1038/s42003-026-11092-0","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s42003-026-11092-0","archive_url":"https://space-kitty.com/papers/doi:10.1038/s42003-026-11092-0","updated":null,"pmid":"42919899","pmcid":"PMC13694708","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13694708/pdf","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_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Dysregulation of the Hippo pathway enhances PD-L2 transcription to promote immune evasion in head and neck squamous cell carcinoma\" by Ando T, Okamoto K, Sato K et al., https://doi.org/10.1038/s42003-026-11092-0, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"cancer-immunotherapy","name":"Cancer Immunotherapy","domain_slug":"medicine"}],"cited_in_dossiers":[]}