Poorly immunogenic tumor cells evade host immunity and grow even in the presence of an intact immune system, but the complex mechanisms regulating tumor immunogenicity have not been elucidated. Here, we discovered an unexpected role of the Hippo pathway in suppressing anti-tumor immunity. We demonstrate that, in three different murine syngeneic tumor models (B16, SCC7, and 4T1), loss of the Hippo pathway kinases LATS1/2 (large tumor suppressor 1 and 2) in tumor cells inhibits tumor growth. Tumor regression by LATS1/2 deletion requires adaptive immune responses, and LATS1/2 deficiency enhances tumor vaccine efficacy. Mechanistically, LATS1/2-null tumor cells secrete nucleic-acid-rich extracellular vesicles, which induce a type I interferon response via the Toll-like receptors-MYD88/TRIF pathway. LATS1/2 deletion in tumors thus improves tumor immunogenicity, leading to tumor destruction by enhancing anti-tumor immune responses. Our observations uncover a key role of the Hippo pathway in modulating tumor immunogenicity and demonstrate a proof of concept for targeting LATS1/2 in cancer immunotherapy.
Pubmed ID: 27912060 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Computable knowledge regarding functions of genes and gene products. GO resources include biomedical ontologies that cover molecular domains of all life forms as well as extensive compilations of gene product annotations to these ontologies that provide largely species-neutral, comprehensive statements about what gene products do. Used to standardize representation of gene and gene product attributes across species and databases.
View all literature mentionsThis monoclonal targets CD81
View all literature mentionsThis recombinant monoclonal targets YAP
View all literature mentionsThis polyclonal targets YAP1
View all literature mentionsThis monoclonal targets Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Asp362 of human TAZ protein
View all literature mentionsThis monoclonal targets LATS1
View all literature mentionsThis monoclonal targets Pdcd6ip
View all literature mentionsThis monoclonal targets CD16 / CD32
View all literature mentionsThis monoclonal targets IL-12 (p40 / p70)
View all literature mentionsThis monoclonal targets IL-12
View all literature mentionsThis polyclonal targets Ovalbumin
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis monoclonal targets Actin
View all literature mentionsThis monoclonal targets Hsp90
View all literature mentionsThis monoclonal targets Flotillin-1
View all literature mentionsThis unknown targets LATS1/LATS2
View all literature mentionsThis monoclonal targets YAP (63.7)
View all literature mentionsCell line B16-F10 is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line 4T1 is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line EL4 is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name C3H/HeOuJ from IMSR.
View all literature mentionsMus musculus with name BALB/cJ from IMSR.
View all literature mentionsMus musculus with name B6;129S7-Rag1tm1Mom/J from IMSR.
View all literature mentionsMus musculus with name B6(Cg)-Sting1tm1.2Camb/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6-Tg(TcraTcrb)1100Mjb/J from IMSR.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsSoftware for identifying, characterizing, and quantifying proteins in biological samples. Can be used for range of proteomics workflows such as protein and peptide identification, PTM analysis, and isobaric mass tagging for quantification. Supports multiple database search algorithms and multiple dissociation techniques.
View all literature mentions