SIRT1 limits the function and fate of myeloid-derived suppressor cells in tumors by orchestrating HIF-1α-dependent glycolysis

Cancer Research
Guangwei LiuYiwei Chu

Abstract

Myeloid-derived suppressor cells (MDSC) display an immature phenotype that may assume a classically activated (M1) or alternatively activated phenotype (M2) in tumors. In this study, we investigated metabolic mechanisms underlying the differentiation of MDSCs into M1 or M2 myeloid lineage and their effect on cancer pathophysiology. We found that SIRT1 deficiency in MDSCs directs a specific switch to M1 lineage when cells enter the periphery from bone marrow, decreasing the suppressive function in favor of a proinflammatory M1 phenotype associated with tumor cell attack. Glycolytic activation through the mTOR-hypoxia-inducible factor-1α (HIF-1α) pathway was required for differentiation to the M1 phenotype, which conferred protection against tumors. Our results define the essential nature of a SIRT1-mTOR/HIF-1α glycolytic pathway in determining MDSC differentiation, with implications for metabolic reprogramming as a cancer therapeutic approach.

References

Mar 12, 2003·Cell·Thorsten CramerRandall S Johnson
Feb 24, 1956·Science·O WARBURG
Jan 5, 2005·The Journal of Experimental Medicine·Sarah R WalmsleyEdwin R Chilvers
Jun 2, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Guangwei LiuYong Zhao
Jun 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Carole PeyssonnauxVictor Nizet
Jan 25, 2008·Nature Reviews. Molecular Cell Biology·Matthias P Wymann, Roger Schneiter
Jul 18, 2008·Nature Reviews. Cancer·Craig MurdochClaire E Lewis
Aug 9, 2008·Experimental Cell Research·Jedon SequeiraMichael W McBurney
Oct 18, 2008·Immunobiology·Laila ElbarghatiClaire E Lewis
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·J A EhsesM Y Donath
Sep 5, 2009·The Journal of Clinical Investigation·Jinping ZhangDeyu Fang
Feb 20, 2010·PloS One·Hiyaa Singhee GhoshPaul D Robbins
Feb 23, 2010·Current Opinion in Immunology·Elisa PeranzoniVincenzo Bronte
Jul 22, 2010·Molecular and Cellular Biology·Thaddeus T SchugXiaoling Li
Sep 30, 2010·The Journal of Experimental Medicine·Cesar A CorzoDmitry I Gabrilovich
Oct 26, 2010·Trends in Molecular Medicine·Matthew P GillumGerald I Shulman
Nov 12, 2010·Trends in Immunology·Thomas Condamine, Dmitry I Gabrilovich
Jan 5, 2011·Molecular and Cellular Biology·Ulf H BeierWayne W Hancock
Jun 8, 2011·The Journal of Clinical Investigation·Laetitia A MautiIvan Stamenkovic
Jun 10, 2011·The New England Journal of Medicine·Leonard Guarente
Sep 24, 2011·Nature Reviews. Cancer·Gemma K Alderton
Sep 29, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Agnieszka LegutkoFabrice Bureau
Jan 6, 2012·Proceedings of the National Academy of Sciences of the United States of America·Beixue GaoDeyu Fang
Aug 16, 2012·The Journal of Biological Chemistry·Yolanda AlvarezMariano Sánchez Crespo
Oct 12, 2012·PloS One·Luís MartinsCarlos Diéguez
Mar 28, 2013·Journal of Molecular Cell Biology·Wen-Chin YangPing-Ying Pan

❮ Previous
Next ❯

Citations

Jun 2, 2015·Expert Review of Clinical Immunology·Hui YangGuangwei Liu
Dec 25, 2015·Nature Reviews. Rheumatology·Andras Perl
Mar 3, 2015·Proceedings of the National Academy of Sciences of the United States of America·Guangwei LiuRuifu Yang
Apr 12, 2016·Frontiers in Immunology·Yannick De VlaeminckKarine Breckpot
Aug 15, 2014·Frontiers in Immunology·Tingting WangRuoning Wang
Dec 3, 2016·Cancer Gene Therapy·M Pergamo, G Miller
Jan 5, 2017·ACS Chemical Biology·Rebecca L HancockAkane Kawamura
Feb 15, 2017·Endocrine-related Cancer·Andrew M K LawDavid Gallego-Ortega
Feb 10, 2016·Trends in Immunology·Vinit KumarDmitry I Gabrilovich
Aug 5, 2015·Seminars in Cell & Developmental Biology·Carlos Sebastián, Raul Mostoslavsky
Mar 24, 2018·Cellular & Molecular Immunology·Eslam MohamedPaulo C Rodriguez
Jun 20, 2018·The Journal of Clinical Investigation·Themis AlissafiPanayotis Verginis
Jul 12, 2018·International Journal of Cancer. Journal International Du Cancer·Zhongnan YinLixiang Xue
Jan 25, 2018·Oncogenesis·Varvara PetrovaIvano Amelio
Mar 31, 2019·Molecular Cancer·Wanrong MengGuiquan Zhu
Jun 1, 2019·Expert Review of Anticancer Therapy·Veethika Pandey, Peter Storz
Jun 9, 2019·International Journal of Molecular Sciences·Giovanni StalloneGiuseppe Grandaliano
Sep 10, 2014·Immunology·Vinit Kumar, Dmitry I Gabrilovich
Feb 11, 2020·Human Vaccines & Immunotherapeutics·Ningbo Zheng, Yong Lu
Mar 4, 2020·Cells·Andrew M K LawDavid Gallego-Ortega
Apr 3, 2020·Antioxidants & Redox Signaling·Cassandra M Moshfegh, Adam J Case
Jan 23, 2018·Frontiers in Immunology·Anca Dorhoi, Nelita Du Plessis
May 28, 2019·Frontiers in Immunology·Francesca Maria ConsonniAntonio Sica
Sep 19, 2020·Cancers·Yufei WangGuangwei Liu
Sep 29, 2020·Frontiers in Immunology·Elliot D Kramer, Scott I Abrams
Aug 8, 2018·International Journal of Molecular Sciences·Andrew J BryantLyle L Moldawer
Jul 31, 2018·Journal of Immunology Research·Fan YangYong Zhao
Jan 6, 2019·Cells·Fahd BoutoujaHarald W Platta
Aug 9, 2020·International Journal of Molecular Sciences·Chiara Corrado, Simona Fontana
Jul 24, 2020·Cellular & Molecular Immunology·Xingyi Pan, Lei Zheng
Oct 23, 2019·World Journal of Gastroenterology : WJG·Meng-Ting RenChen-Yan Ding

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

Cancer Metabolic Reprogramming (Keystone)

Cancer metabolic reprogramming is important for the rapid growth and proliferation of cancer cells. Cancer cells have the ability to change their metabolic demands depending on their environment, regulated by the activation of oncogenes or loss of tumor suppressor genes. Here is the latest research on cancer metabolic reprogramming.

Cancer Metabolic Reprogramming

Cancer metabolic reprogramming is important for the rapid growth and proliferation of cancer cells. Cancer cells have the ability to change their metabolic demands depending on their environment, regulated by the activation of oncogenes or loss of tumor suppressor genes. Here is the latest research on cancer metabolic reprogramming.