title: Deficiency of AMPK in CD8+ T cells suppresses their anti-tumor function by inducing protein phosphatase-mediated cell death.
abstract: A number of studies have linked AMPK, a major metabolic sensor coordinating of multiple cellular functions, to tumor development and progression. However, the exact role of AMPK in tumor development is still controversial. Here we report that activation of AMPK promotes survival and anti-tumor function of T cells, in particular CD8+ T cells, resulting in superior tumor suppression in vivo. While AMPK expression is dispensable for T cell development, genetic deletion of AMPK promotes T cell death during in vitro activation and in vivo tumor development. Moreover, we demonstrate that protein phosphatases are the key mediators of AMPK-dependent effects on T cell death, and inhibition of phosphatase activity by okadaic acid successfully restores T cell survival and function. Altogether, our data suggest a novel mechanism by which AMPK regulates protein phosphatase activity in control of survival and function of CD8+ T cells, thereby enhancing their role in tumor immunosurveillance.
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: Enyu
authors.initials: E
authors.lastname: Rao
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: Ganqian
authors.initials: G
authors.lastname: Zhu
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: Jiaqing
authors.initials: J
authors.lastname: Hao
authors.affiliation: Center for Clinical and Translational Science Metabolomics Core, Mayo Clinic, Rochester, MN, USA.
authors.forename: Xuan-Mai T
authors.initials: XM
authors.lastname: Persson
authors.affiliation: Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA.
authors.forename: Nejat K
authors.initials: NK
authors.lastname: Egilmez
authors.affiliation: Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Suttles
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000172:deficiency* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*
chemical_list: D055372:AMP-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases
keywords: AMPK; CD8+ T cells; T cell survival; anti-tumor function