The Hippo Pathway Kinases LATS1/2 Suppress Cancer Immunity.

Abstract	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.
Authors	Toshiro Moroishi, Tomoko Hayashi, Wei-Wei Pan, Yu Fujita, Matthew V Holt, Jun Qin, Dennis A Carson, Kun-Liang Guan
Journal	Cell (Cell) Vol. 167 Issue 6 Pg. 1525-1539.e17 (Dec 01 2016) ISSN: 1097-4172 [Electronic] United States
PMID	27912060 (Publication Type: Journal Article)
Copyright	Copyright Â© 2016 Elsevier Inc. All rights reserved.
Chemical References	Cancer Vaccines Toll-Like Receptors Tumor Suppressor Proteins Lats1 protein, mouse LATS2 protein, mouse Protein Serine-Threonine Kinases
Topics	Animals Cancer Vaccines (immunology) Gene Deletion Immune Tolerance Immunotherapy Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Inbred C57BL Neoplasms (immunology) Protein Serine-Threonine Kinases (genetics, metabolism) Signal Transduction Toll-Like Receptors (metabolism) Tumor Suppressor Proteins (genetics, metabolism)

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