Deficiency of AMPK in CD8+ T cells suppresses their anti-tumor function by inducing protein phosphatase-mediated cell death

Oncotarget
Enyu RaoBing Li

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.

References

Mar 10, 1995·Science·S Nagata, P Golstein
Sep 11, 2001·Biochemical and Biophysical Research Communications·S L ChoiJ Ha
Mar 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Naoko SekiThomas J Sayers
Oct 31, 2002·Nature Immunology·Gavin P DunnRobert D Schreiber
Aug 17, 2004·Immunity·Gavin P DunnRobert D Schreiber
Dec 4, 2004·The EMBO Journal·Jing YangDavid Barford
Jun 21, 2005·Springer Seminars in Immunopathology·Mara Gerloni, Maurizio Zanetti
Jan 5, 2006·Genes & Development·Wei-Xing Zong, Craig B Thompson
May 16, 2006·Apoptosis : an International Journal on Programmed Cell Death·Stephanie SchwarzJosef Krieglstein
Jul 5, 2006·The Journal of Experimental Medicine·Peter TamásDoreen A Cantrell
Jul 13, 2006·The Journal of Biological Chemistry·Milica MomcilovicMarian Carlson
May 4, 2007·The Journal of Clinical Investigation·Jeremy B Swann, Mark J Smyth
Oct 31, 2008·Nature Reviews. Molecular Cell Biology·Guido Kroemer, Beth Levine
Dec 4, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Duygu SagJill Suttles
Mar 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mehmet O KilincNejat K Egilmez
Apr 18, 2009·Molecular Cancer Therapeutics·Hyeon Ung ParkSean P Collins
Aug 24, 2010·The Journal of Biological Chemistry·Jaroslaw W ZmijewskiEdward Abraham
Jan 15, 2011·Nature Reviews. Immunology·David Finlay, Doreen A Cantrell
Jan 25, 2011·Nature Cell Biology·Joungmok KimKun-Liang Guan
Mar 18, 2011·Nature·Marcus E Peter
Apr 13, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sahar M A MahmoudAndrew R Green
Apr 15, 2011·Nature·D Grahame Hardie
May 3, 2011·Neoplasia : an International Journal for Oncology Research·Ramandeep RattanViji Shridhar
May 11, 2011·The Journal of Clinical Investigation·Lukas BaitschDaniel E Speiser
Sep 21, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nancie J MacIverRussell G Jones
Aug 15, 2012·Immunological Reviews·Julianna BlagihRussell G Jones
Jan 1, 2013·Cell Metabolism·Brandon FaubertRussell G Jones
Jan 12, 2013·European Journal of Immunology·Julia RolfDoreen A Cantrell
Mar 19, 2013·European Journal of Immunology·Koichi Araki, Rafi Ahmed
Mar 21, 2013·Current Opinion in Immunology·Glenn Dranoff, Douglas Fearon
May 17, 2013·Cellular Logistics·Sang-Min Jeon, Nissim Hay
Jul 26, 2013·Journal of Leukocyte Biology·Kelly Casey CarrollJill Suttles
Dec 19, 2013·Nature Chemical Biology·Scott J Dixon, Brent R Stockwell
Apr 30, 2014·Cancer Immunology Research·Hye-Jung Kim, Harvey Cantor
Jun 28, 2014·Oncotarget·Calvin TebbeRamandeep Rattan

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Citations

Feb 13, 2016·Frontiers in Immunology·Barbara MolonAntonella Viola
Apr 7, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xiaoling HeDeqiang Huang
Jun 6, 2019·Nature Communications·Luigi RacioppiDonald P McDonnell
Dec 19, 2019·Frontiers in Immunology·Cansu YerindeCarl Weidinger
Dec 29, 2019·International Journal of Molecular Sciences·Shamir Cassim, Jacques Pouyssegur
Jun 9, 2016·European Journal of Immunology·Marie BettonvilleMichel Y Braun
Jun 9, 2020·Frontiers in Cell and Developmental Biology·Mehdi ChaibLiza Makowski
Jun 30, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ashutosh K MangalamShailendra Giri
Mar 25, 2017·Frontiers in Immunology·Jun WeiHongbo Chi
Nov 12, 2017·Science China. Life Sciences·Jing WangXuemei Qin
Nov 11, 2020·ELife·Jefte M DrijversMarcia C Haigis
Nov 6, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shawna K BrookensMark R Boothby
Oct 30, 2020·Metabolites·Wesley H Godfrey, Michael D Kornberg
Mar 15, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Katharina A MayerGerhard J Zlabinger
Apr 9, 2021·Nature Reviews. Nephrology·Paulo José BassoNiels Olsen Saraiva Câmara

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Methods Mentioned

BETA
PCR
PMA
flow cytometry
ELISA

Software Mentioned

Flowjo

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