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Enhanced cytotoxic T‐cell function and inhibition of tumor progression by Mst1 deficiency
Author(s) -
Yasuda Kaneki,
Ueda Yoshihiro,
Ozawa Madoka,
Matsuda Tadashi,
Kinashi Tatsuo
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12045
Subject(s) - cytotoxic t cell , granzyme b , cytotoxicity , cancer research , granzyme , immunotherapy , chemistry , apoptosis , biology , perforin , in vitro , microbiology and biotechnology , immunology , immune system , biochemistry
Mammalian ste‐20 like kinase Mst1 plays important roles during apoptosis, proliferation, cell polarity, and migration. Here, we report a novel role of Mst1 for cytotoxic T‐cell responses and tumor suppression. The defect of Mst1 caused decreased levels of FoxO, and promoted cytotoxicity in vitro . Mst1 −/− cytotoxic T cells also exhibited enhanced T‐bet expression that was associated with elevated expression levels of IFN γ and granzyme B. Moreover, Mst1 −/− cytotoxic T cells suppressed tumor growth in vivo . The data suggest that Mst1 inhibits cytotoxicity via T‐bet suppression by FoxO1 and FoxO3a. Thus, Mst1 is a potential therapeutic target for tumor immunotherapy.