A glutamine 'tug-of-war': targets to manipulate glutamine metabolism for cancer immunotherapy

被引：23
作者：
Pallett, Laura J. [1 ]
Dimeloe, Sarah [2 ]
Sinclair, Linda V. [3 ]
Byrne, Adam J. [4 ]
Schurich, Anna [5 ]
机构：
[1] UCL, Inst Immun & Transplantat, Div Infect & Immun, Rayne Bldg,5 Univ St, London WC1E 6JF, England
[2] Univ Birmingham, Inst Immunol & Immunotherapy, Inst Metab & Syst Res, Coll Med & Dent Sci, Birmingham, W Midlands, England
[3] Univ Dundee, Sch Life Sci, Div Cell Signalling & Immunol, Dundee, Scotland
[4] Imperial Coll London, Natl Heart & Lung Inst, Inflammat Repair & Dev Sect, London, England
[5] Kings Coll London, Sch Immunol & Microbial Sci, Dept Infect Dis, London, England
来源：
IMMUNOTHERAPY ADVANCES | 2021年 / 1卷 / 01期
基金：
英国惠康基金;
关键词：
glutamine; T cells; cancer immunotherapy; PHASE-II; MAMMALIAN-CELLS; ACTIVATION; INHIBITION; GROWTH; EXPRESSION; TRANSPORT; 6-DIAZO-5-OXO-L-NORLEUCINE; ANTIPORTER; PROTEINS;
D O I：
10.1093/immadv/ltab010
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Within the tumour microenvironment (TME), there is a cellular 'tug-of-war' for glutamine, the most abundant amino acid in the body. This competition is most evident when considering the balance between a successful anti-tumour immune response and the uncontrolled growth of tumour cells that are addicted to glutamine. The differential effects of manipulating glutamine abundance in individual cell types is an area of intense research and debate. Here, we discuss some of the current strategies in development altering local glutamine availability focusing on inhibition of enzymes involved in the utilisation of glutamine and its uptake by cells in the TME. Further studies are urgently needed to complete our understanding of glutamine metabolism, to provide critical insights into the pathways that represent promising targets and for the development of novel therapeutic strategies for the treatment of advanced or drug resistant cancers.
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页数：9
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共 75 条
[1]   From Krebs to clinic: glutamine metabolism to cancer therapy [J].
Altman, Brian J. ;
Stine, Zachary E. ;
Dang, Chi V. .
NATURE REVIEWS CANCER, 2016, 16 (10) :619-634
[2]   Cystine-glutamate antiporter xCT deficiency suppresses tumor growth while preserving antitumor immunity [J].
Arensman, Michael D. ;
Yang, Xiaoran S. ;
Leahy, Danielle M. ;
Toral-Barza, Lourdes ;
Mileski, Mary ;
Rosfjord, Edward C. ;
Wang, Fang ;
Deng, Shibing ;
Myers, Jeremy S. ;
Abraham, Robert T. ;
Eng, Christina H. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2019, 116 (19) :9533-9542
[3]   Compensatory metabolic networks in pancreatic cancers upon perturbation of glutamine metabolism [J].
Biancur, Douglas E. ;
Paulo, Joao A. ;
Malachowska, Beata ;
Del Rey, Maria Quiles ;
Sousa, Cristovao M. ;
Wang, Xiaoxu ;
Sohn, Albert S. W. ;
Chu, Gerald C. ;
Gygi, Steven P. ;
Harper, J. Wade ;
Fendler, Wojciech ;
Mancias, Joseph D. ;
Kimmelman, Alec C. .
NATURE COMMUNICATIONS, 2017, 8
[4]   The Energy Sensor AMPK Regulates T Cell Metabolic Adaptation and Effector Responses In Vivo [J].
Blagih, Julianna ;
Coulombe, Francois ;
Vincent, Emma E. ;
Dupuy, Fanny ;
Galicia-Vazquez, Gabriela ;
Yurchenko, Ekaterina ;
Raissi, Thomas C. ;
van der Windt, Gerritje J. W. ;
Viollet, Benoit ;
Pearce, Erika L. ;
Pelletier, Jerry ;
Piccirillo, Ciriaco A. ;
Krawczyk, Connie M. ;
Divangahi, Maziar ;
Jones, Russell G. .
IMMUNITY, 2015, 42 (01) :41-54
[5]   Disruption of Amino Acid Homeostasis by Novel ASCT2 Inhibitors Involves Multiple Targets [J].
Broer, Angelika ;
Fairweather, Stephen ;
Broer, Stefan .
FRONTIERS IN PHARMACOLOGY, 2018, 9
[6]   Amino acid homeostasis and signalling in mammalian cells and organisms [J].
Broer, Stefan ;
Broer, Angelika .
BIOCHEMICAL JOURNAL, 2017, 474 :1935-1963
[7]   Inhibition of Glutamine Utilization Synergizes with Immune Checkpoint Inhibitor to Promote Antitumor Immunity [J].
Byun, Jun-Kyu ;
Park, Mihyang ;
Lee, Seunghyeong ;
Yun, Jae Won ;
Lee, Jaebon ;
Kim, Jae Sun ;
Cho, Sung Jin ;
Jeon, Hui-Jeon ;
Lee, In-Kyu ;
Choi, Yeon-Kyung ;
Park, Keun-Gyu .
MOLECULAR CELL, 2020, 80 (04) :592-+
[8]   Glutamine Uptake and Metabolism Are Coordinately Regulated by ERK/MAPK during T Lymphocyte Activation [J].
Carr, Erikka L. ;
Kelman, Alina ;
Wu, Glendon S. ;
Gopaul, Ravindra ;
Senkevitch, Emilee ;
Aghvanyan, Anahit ;
Turay, Achmed M. ;
Frauwirth, Kenneth A. .
JOURNAL OF IMMUNOLOGY, 2010, 185 (02) :1037-1044
[9]   Mitochondrial localization and structure-based phosphate activation mechanism of Glutaminase C with implications for cancer metabolism [J].
Cassago, Alexandre ;
Ferreira, Amanda P. S. ;
Ferreira, Igor M. ;
Fornezari, Camila ;
Gomes, Emerson R. M. ;
Greene, Kai Su ;
Pereira, Humberto M. ;
Garratt, Richard C. ;
Dias, Sandra M. G. ;
Ambrosio, Andre L. B. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (04) :1092-1097
[10]   Group I mGlu receptor stimulation inhibits activation-induced cell death of human T lymphocytes [J].
Chiocchetti, Annalisa ;
Miglio, Gianluca ;
Mesturini, Riccardo ;
Varsaldi, Federica ;
Mocellin, Marco ;
Orilieri, Elisabetta ;
Dianzani, Chiara ;
Fantozzi, Roberto ;
Dianzani, Umberto ;
Lombardi, Grazia .
BRITISH JOURNAL OF PHARMACOLOGY, 2006, 148 (06) :760-768
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