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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Review Article

肿瘤诱导代谢和T细胞在肿瘤环境中的定位

卷 20, 期 10, 2020

页: [741 - 756] 页: 16

弟呕挨: 10.2174/1568009620666200720010647

价格: $65

摘要

肿瘤环境中有几种T细胞的亚型，每一种都使用不同的代谢机制来提供能量。由于癌细胞需要高水平的葡萄糖，在肿瘤环境中的食物匮乏会导致免疫细胞失活，特别是T 效应细胞，因为这些细胞在活动的早期阶段需要葡萄糖。不同的信号通路，如PI3K-AKt-mTOR、MAPK、HIF-1α等，被激活或灭活的能量来源的数量和类型或氧水平，决定了T细胞在癌变环境的命运。本文综述了肿瘤环境中的代谢产物及其对T细胞功能的影响。它也解释了T细胞在肿瘤和正常情况下的信号通路，由于可获得的代谢产物和肿瘤环境中的T细胞亚型的水平。

关键词: 癌症，T淋巴细胞，代谢，免疫治疗，免疫逃避，细胞因子

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[1]
Molon, B.; Calì, B.; Viola, A. T Cells and cancer: How metabolism shapes immunity. Front. Immunol., 2016, 7, 20.
[http://dx.doi.org/10.3389/fimmu.2016.00020] [PMID: 26870036]
[2]
Jung, J.; Zeng, H.; Horng, T. Metabolism as a guiding force for immunity. Nat. Cell Biol., 2019, 21(1), 85-93.
[http://dx.doi.org/10.1038/s41556-018-0217-x] [PMID: 30602764]
[3]
Bantug, G.R.; Galluzzi, L.; Kroemer, G.; Hess, C.J.N.R.I. The spectrum of T cell metabolism in health and disease. Nat. Rev. Immunol., 2018, 18(1), 19.
[http://dx.doi.org/10.1038/nri.2017.99]
[4]
Marelli-Berg, F.M.; Fu, H.; Mauro, C. Molecular mechanisms of metabolic reprogramming in proliferating cells: implications for T-cell-mediated immunity. Immunology, 2012, 136(4), 363-369.
[http://dx.doi.org/10.1111/j.1365-2567.2012.03583.x] [PMID: 22384794]
[5]
Grivennikov, S.I.; Greten, F.R.; Karin, M. Immunity, inflammation, and cancer. Cell, 2010, 140(6), 883-899.
[http://dx.doi.org/10.1016/j.cell.2010.01.025] [PMID: 20303878]
[6]
Byrne, K.T.; Vonderheide, R.H.; Jaffee, E.M.; Armstrong, T.D. Special conference on tumor immunology and immunotherapy: A new chapter. Cancer Immunol. Res., 2015, 3(6), 590-597.
[http://dx.doi.org/10.1158/2326-6066.CIR-15-0106] [PMID: 25968457]
[7]
Sautès-Fridman, C. Tumor immunology, toward a success story? Front. Immunol., 2015, 6, 65.
[PMID: 25741340]
[8]
Nandi, D.; Pathak, S.; Verma, T.; Singh, M.; Chattopadhyay, A.; Thakur, S.; Raghavan, A.; Gokhroo, A. Vijayamahantesh, T cell costimu-lation, checkpoint inhibitors and anti-tumor therapy. J. Biosci., 2020, 45(1), 1-36.
[http://dx.doi.org/10.1007/s12038-020-0020-2] [PMID: 32345776]
[9]
Klein Geltink, R.I.; Kyle, R.L.; Pearce, E.L.J.A.i. Unraveling the complex interplay between T cell metabolism and function. Annu. Rev. Immunol., 2018, 36, 461-488.
[http://dx.doi.org/10.1146/annurev-immunol-042617-053019]
[10]
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: the next generation. Cell, 2011, 144(5), 646-674.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[11]
Phan, L.M.; Yeung, S.C.; Lee, M.H. Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies. Cancer Biol. Med., 2014, 11(1), 1-19.
[PMID: 24738035]
[12]
Mellor, A.L.; Munn, D.H. Creating immune privilege: active local suppression that benefits friends, but protects foes. Nat. Rev. Immunol., 2008, 8(1), 74-80.
[http://dx.doi.org/10.1038/nri2233] [PMID: 18064049]
[13]
Icard, P.; Shulman, S.; Farhat, D.; Steyaert, J.-M.; Alifano, M.; Lincet, H. J. D. R. U. How the Warburg effect supports aggressiveness and drug resistance of cancer cells? 2018, 38, 1-11.
[14]
Hall, A.; Meyle, K.D.; Lange, M.K.; Klima, M.; Sanderhoff, M.; Dahl, C.; Abildgaard, C.; Thorup, K.; Moghimi, S.M.; Jensen, P.B.; Bartek, J.; Guldberg, P.; Christensen, C. Dysfunctional oxidative phosphorylation makes malignant melanoma cells addicted to glycolysis driven by the (V600E) BRAF oncogene. Oncotarget, 2013, 4(4), 584-599.
[http://dx.doi.org/10.18632/oncotarget.965] [PMID: 23603840]
[15]
Haq, R.; Shoag, J.; Andreu-Perez, P.; Yokoyama, S.; Edelman, H.; Rowe, G.C.; Frederick, D.T.; Hurley, A.D.; Nellore, A.; Kung, A.L.; Wargo, J.A.; Song, J.S.; Fisher, D.E.; Arany, Z.; Widlund, H.R. Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF. Cancer Cell, 2013, 23(3), 302-315.
[http://dx.doi.org/10.1016/j.ccr.2013.02.003] [PMID: 23477830]
[16]
Trucco, L.D.; Mundra, P.A.; Garcia-Martinez, P.; Hogan, K.; Dhomen, N.; Pavet, V.; Marais, R. Melanocyte specific deletion of Map3k1 reveals its role in BRAFV600E-driven melanoma ; AACR; , 2019.
[17]
Cham, C.M.; Driessens, G.; O’Keefe, J.P.; Gajewski, T.F. Glucose deprivation inhibits multiple key gene expression events and effector functions in CD8+ T cells. Eur. J. Immunol., 2008, 38(9), 2438-2450.
[http://dx.doi.org/10.1002/eji.200838289] [PMID: 18792400]
[18]
Danhier, P.; Bański, P.; Payen, V.L.; Grasso, D.; Ippolito, L.; Sonveaux, P.; Porporato, P.E. Cancer metabolism in space and time: be-yond the Warburg effect. Biochim. Biophys. Acta, 2017, 1858(8), 556-572.
[http://dx.doi.org/10.1016/j.bbabio.2017.02.001]
[19]
Gerriets, V.A.; Kishton, R.J.; Nichols, A.G.; Macintyre, A.N.; Inoue, M.; Ilkayeva, O.; Winter, P.S.; Liu, X.; Priyadharshini, B.; Slawinska, M.E.; Haeberli, L. Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation. J. Clin. Invest., 2015, 125(1), 194-207.
[20]
Fischer, K.; Hoffmann, P.; Voelkl, S.; Meidenbauer, N.; Ammer, J.; Edinger, M.; Gottfried, E.; Schwarz, S.; Rothe, G.; Hoves, S.J.B. Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood, 2007, 109(9), 3812-3819.
[http://dx.doi.org/10.1182/blood-2006-07-035972]
[21]
Fukumura, D.; Xu, L.; Chen, Y.; Gohongi, T.; Seed, B.; Jain, R.K. Hypoxia and acidosis independently up-regulate vascular endothelial growth factor transcription in brain tumors in vivo. Cancer Res., 2001, 61(16), 6020-6024.
[22]
Michalek, R.D.; Gerriets, V.A.; Jacobs, S.R.; Macintyre, A.N.; MacIver, N.J.; Mason, E.F.; Sullivan, S.A.; Nichols, A.G.; Rathmell, J.C. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J. Immunol., 2011, 1003613.
[23]
Kim, C.H. Regulatory T-Cells and Th17 cells in tumor microenvironment. cancer immunology ; Springer; , 2020, pp. pp. 91-106.
[24]
Chang, C.H.; Qiu, J.; O’Sullivan, D.; Buck, M.D.; Noguchi, T.; Curtis, J.D.; Chen, Q.; Gindin, M.; Gubin, M.M.; Van Der Windt, G.J.; Tonc, E. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell, 2015, 162(6), 1229-1241.
[http://dx.doi.org/10.1016/j.cell.2015.08.016]
[25]
Cham, C.M.; Gajewski, T.F. Glucose availability regulates IFN-γ production and p70S6 kinase activation in CD8+ effector T cells. J. Immunol., 2005, 174(8), 4670-4677.
[26]
Cham, C.M.; Driessens, G.; O’Keefe, J.P.; Gajewski, T.F. Glucose deprivation inhibits multiple key gene expression events and effector functions In CD8+ T cells. Eur. J. Immunol., 2008, 38(9), 2438-2450.
[27]
Jacobs, S.R.; Herman, C.E.; MacIver, N.J.; Wofford, J.A.; Wieman, H.L.; Hammen, J.J.; Rathmell, J.C. Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways. J. Immunol., 2008, 180(7), 4476-4486.
[http://dx.doi.org/10.4049/jimmunol.180.7.4476]
[28]
Macintyre, A.N.; Gerriets, V.A.; Nichols, A.G.; Michalek, R.D.; Rudolph, M.C.; Deoliveira, D.; Anderson, S.M.; Abel, E.D.; Chen, B.J.; Hale, L.P.; Rathmell, J.C. How the Warburg effect supports aggressiveness and drug resistance of cancer cells? Cell Metabol., 2014, 1(11), 61-72.
[29]
Frauwirth, K.A.; Thompson, C.B. Regulation of T lymphocyte metabolism. J. Immunol., 2004, 172(8), 4661-4665.
[30]
Chellappa, S.; Kushekhar, K.; Munthe, L. A.; Tjonnfjord, G. E.; Aandahl, E. M.; Okkenhaug, K.; Tasken, K. The PI3K p110delta isoform inhibitor idelalisib preferentially inhibits human regulatory T cell function. J. immunology (Baltimore, Md.: 1950), 2019, 202(5), 1397-1405.
[31]
Qiu, J.; Villa, M.; Sanin, D.E.; Buck, M.D.; O’Sullivan, D.; Ching, R.; Matsushita, M.; Grzes, K.M.; Winkler, F.; Chang, C-H. Acetate promotes T cell effector function during glucose restriction. Cell Rep., 2019, 27(7), 2063-2074.
[http://dx.doi.org/10.1016/j.celrep.2019.04.022]
[32]
Currie, E.; Schulze, A.; Zechner, R.; Walther, T.C.; Farese, R.V., Jr Cellular fatty acid metabolism and cancer. Cell Metabol., 2013, 18(2), 153-161.
[33]
Zhang, F.; Du, G. Dysregulated lipid metabolism in cancer. World J. Biol. Chem., 2012, 3(8), 167.
[http://dx.doi.org/10.4331/wjbc.v3.i8.167]
[34]
Zhang, F.; Du, G. Adipose tissue-derived progenitor cells and cancer. World J. Biol. Chem., 2010, 2(5), 103.
[http://dx.doi.org/10.4252/wjsc.v2.i5.103]
[35]
Byersdorfer, C.A.; Tkachev, V.; Opipari, A.W.; Goodell, S.; Swanson, J.; Sandquist, S.; Glick, G.D.; Ferrara, J.L. Effector T cells require fatty acid metabolism during murine graft-versus-host disease Blood, 2013. 2013-04-495515
[36]
Byersdorfer, C.A. The role of fatty acid oxidation in the metabolic reprograming of activated T-cells. Front. Immunol., 2014, 5, 641.
[37]
Takahashi, S.; Iizumi, T.; Mashima, K.; Abe, T.; Suzuki, N. Roles and regulation of ketogenesis in cultured astroglia and neurons under hypoxia and hypoglycemia. 2014, 6(5), 175. 9091414550997
[38]
Altman, B.J.; Stine, Z.E.; Dang, C.V. From Krebs to clinic: glutamine metabolism to cancer therapy Nat. Rev. Cancer, 2016, 16(10), 619.
[39]
Hensley, C.T.; Wasti, A.T.; DeBerardinis, R.J. Glutamine and cancer: cell biology, physiology, and clinical opportunities. 2013, 123(9), 3673-3684.
[40]
Villalba, M.; Rathore, M.G.; Lopez-Royuela, N.; Krzywinska, E.; Garaude, J.; Allende-Vega, N. From tumor cell metabolism to tumor immune escape. Int. J. Biochem. Cell Biol., 2013, 45(1), 106-113.
[41]
Mocellin, S.; Bronte, V.; Nitti, D. Nitric oxide, a double edged sword in cancer biology: searching for therapeutic opportunities. Med. Res. Rev., 2007, 27(3), 317-352.
[42]
Tham, M.; Tan, K.W.; Keeble, J.; Wang, X.; Hubert, S.; Barron, L.; Tan, N.S.; Kato, M.; Prevost-Blondel, A.; Angeli, V.; Abastado, J.P. Melanoma-initiating cells exploit M2 macrophage TGFβ and arginase pathway for survival and proliferation. Oncotarget, 2014, 5(23), 12027.
[43]
Kasic, T.; Colombo, P.; Soldani, C.; Wang, C.M.; Miranda, E.; Roncalli, M.; Bronte, V.; Viola, A. Modulation of human T-cell functions by reactive nitrogen species. Eur. J. Immunol., 2011, 41(7), 1843-1849.
[44]
Nagaraj, S.; Gupta, K.; Pisarev, V.; Kinarsky, L.; Sherman, S.; Kang, L.; Herber, D.L.; Schneck, J.; Gabrilovich, D.I. Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat. Med., 2007, 13(7), 828.
[45]
Jones, R.G.; Plas, D.R.; Kubek, S.; Buzzai, M.; Mu, J.; Xu, Y.; Birnbaum, M.J.; Thompson, C.B. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol. Cell, 2005, 18(3), 283-293.
[http://dx.doi.org/10.1016/j.molcel.2005.03.027] [PMID: 15866171]
[46]
Wilke, C.M.; Wu, K.; Zhao, E.; Wang, G.; Zou, W. Prognostic significance of regulatory T cells in tumor. Int. J. Cancer, 2010, 127(4), 748-758.
[http://dx.doi.org/10.1002/ijc.25464] [PMID: 20473951]
[47]
Fuchs, Y.F.; Sharma, V.; Eugster, A.; Kraus, G.; Morgenstern, R.; Dahl, A.; Reinhardt, S.; Petzold, A.; Lindner, A.; Löbel, D.; Bonifacio, E. Gene Expression-Based Identification of Antigen-Responsive CD8(+) T Cells on a Single-Cell Level. Front. Immunol., 2019, 6, 10-2586.
[48]
Shackelford, D.B.; Shaw, R.J. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat. Rev. Cancer, 2009, 9(8), 563-575.
[http://dx.doi.org/10.1038/nrc2676] [PMID: 19629071]
[49]
Michalek, R.D.; Gerriets, V.A.; Jacobs, S.R.; Macintyre, A.N.; MacIver, N.J.; Mason, E.F.; Sullivan, S.A.; Nichols, A.G.; Rathmell, J.C. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J. Immunol., 2011, 186(6), 3299-3303.
[http://dx.doi.org/10.4049/jimmunol.1003613] [PMID: 21317389]
[50]
Blagih, J.; Coulombe, F.; Vincent, E.E.; Dupuy, F.; Galicia-Vázquez, G.; Yurchenko, E.; Raissi, T.C.; van der Windt, G.J.; Viollet, B.; Pearce, E.L.; Pelletier, J.; Piccirillo, C.A.; Krawczyk, C.M.; Divangahi, M.; Jones, R.G. The energy sensor AMPK regulates T cell metabolic adaptation and effector responses in vivo. Immunity, 2015, 42(1), 41-54.
[http://dx.doi.org/10.1016/j.immuni.2014.12.030] [PMID: 25607458]
[51]
Beier, U.H.; Wang, L.; Bhatti, T.R.; Liu, Y.; Han, R.; Ge, G.; Hancock, W.W. Sirtuin-1 targeting promotes Foxp3+ T-regulatory cell func-tion and prolongs allograft survival. Mol. Cell. Biol., 2011, 31(5), 1022-1029.
[http://dx.doi.org/10.1128/MCB.01206-10] [PMID: 21199917]
[52]
Kwon, H-S.; Lim, H.W.; Wu, J.; Schnölzer, M.; Verdin, E.; Ott, M. Three novel acetylation sites in the Foxp3 transcription factor regulate the suppressive activity of regulatory T cells. J. Immunol., 2012, 188(6), 2712-2721.
[http://dx.doi.org/10.4049/jimmunol.1100903] [PMID: 22312127]
[53]
Bulitta, B.; Zuschratter, W.; Bernal, I.; Bruder, D.; Klawonn, F.; von Bergen, M.; Garritsen, H.S.P.; Jänsch, L. Proteomic definition of hu-man mucosal-associated invariant T cells determines their unique molecular effector phenotype. Eur. J. Immunol., 2018, 48(8), 1336-1349.
[http://dx.doi.org/10.1002/eji.201747398] [PMID: 29749611]
[54]
van Loosdregt, J.; Vercoulen, Y.; Guichelaar, T.; Gent, Y.Y.; Beekman, J.M.; van Beekum, O.; Brenkman, A.B.; Hijnen, D-J.; Mutis, T.; Kalkhoven, E.; Prakken, B.J.; Coffer, P.J. Regulation of Treg functionality by acetylation-mediated Foxp3 protein stabilization. Blood, 2010, 115(5), 965-974.
[http://dx.doi.org/10.1182/blood-2009-02-207118] [PMID: 19996091]
[55]
van Loosdregt, J.; Brunen, D.; Fleskens, V.; Pals, C.E.; Lam, E.W.; Coffer, P.J. Rapid temporal control of Foxp3 protein degradation by sirtuin-1. PLoS One, 2011, 6(4), e19047.
[http://dx.doi.org/10.1371/journal.pone.0019047] [PMID: 21533107]
[56]
Wellen, K.E.; Hatzivassiliou, G.; Sachdeva, U.M.; Bui, T.V.; Cross, J.R.; Thompson, C.B. ATP-citrate lyase links cellular metabolism to histone acetylation. Science, 2009, 324(5930), 1076-1080.
[http://dx.doi.org/10.1126/science.1164097] [PMID: 19461003]
[57]
Gavin, M.A.; Rasmussen, J.P.; Fontenot, J.D.; Vasta, V.; Manganiello, V.C.; Beavo, J.A.; Rudensky, A.Y. Foxp3-dependent programme of regulatory T-cell differentiation. Nature, 2007, 445(7129), 771-775.
[http://dx.doi.org/10.1038/nature05543] [PMID: 17220874]
[58]
Hubert, S.; Rissiek, B.; Klages, K.; Huehn, J.; Sparwasser, T.; Haag, F.; Koch-Nolte, F.; Boyer, O.; Seman, M.; Adriouch, S.; Extracellular, N.A.D. Extracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2-P2X7 pathway. J. Exp. Med., 2010, 207(12), 2561-2568.
[http://dx.doi.org/10.1084/jem.20091154] [PMID: 20975043]
[59]
Priyadharshini, B.; Turka, L.A. T-cell energy metabolism as a controller of cell fate in transplantation. Curr. Opin. Organ Transplant., 2015, 20(1), 21-28.
[http://dx.doi.org/10.1097/MOT.0000000000000149] [PMID: 25563988]
[60]
Charbonnier, L.M.; Cui, Y.; Stephen-Victor, E.; Harb, H.; Lopez, D.; Bleesing, J.J.; Garcia-Lloret, M.I.; Chen, K.; Ozen, A. Functional reprogramming of regulatory T cells in the absence of Foxp3. Nat. Immunol., 2019, 20(9), 1208-1219.
[http://dx.doi.org/10.1038/s41590-019-0442-]
[61]
Procaccini, C.; Carbone, F.; Di Silvestre, D.; Brambilla, F.; De Rosa, V.; Galgani, M.; Faicchia, D.; Marone, G.; Tramontano, D.; Corona, M.; Alviggi, C.; Porcellini, A.; La Cava, A.; Mauri, P.; Matarese, G. The proteomic landscape of human ex vivo regulatory and convention-al T cells reveals specific metabolic requirements. Immunity, 2016, 44(2), 406-421.
[http://dx.doi.org/10.1016/j.immuni.2016.01.028] [PMID: 26885861]
[62]
Delgoffe, G.M.; Pollizzi, K.N.; Waickman, A.T.; Heikamp, E.; Meyers, D.J.; Horton, M.R.; Xiao, B.; Worley, P.F.; Powell, J.D. The mam-malian target of rapamycin (mTOR) regulates T helper cell differentiation through the selective activation of mTORC1 and mTORC2 sig-naling. Nat. Immunol., 2011, 12(4), 295.
[http://dx.doi.org/10.1038/ni.2005] [PMID: 21358638]
[63]
Macintyre, A.N.; Gerriets, V.A.; Nichols, A.G.; Michalek, R.D.; Rudolph, M.C.; Deoliveira, D.; Anderson, S.M.; Abel, E.D.; Chen, B.J.; Hale, L.P.; Rathmell, J.C. The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab., 2014, 20(1), 61-72.
[http://dx.doi.org/10.1016/j.cmet.2014.05.004] [PMID: 24930970]
[64]
Cobbold, S.P.; Adams, E.; Farquhar, C.A.; Nolan, K.F.; Howie, D.; Lui, K.O.; Fairchild, P.J.; Mellor, A.L.; Ron, D.; Waldmann, H. Infec-tious tolerance via the consumption of essential amino acids and mTOR signaling. Proc. Natl. Acad. Sci. USA, 2009, 106(29), 12055-12060.
[http://dx.doi.org/10.1073/pnas.0903919106] [PMID: 19567830]
[65]
Newton, R.H.; Lu, Y.; Papa, A.; Whitcher, G.H.; Kang, Y.J.; Yan, C.; Pandolfi, P.P.; Turka, L.A. Suppression of T-cell lymphomagenesis in mice requires PTEN phosphatase activity. Blood, 2015, 125(5), 852-855.
[http://dx.doi.org/10.1182/blood-2014-04-571372] [PMID: 25477498]
[66]
Finlay, D.K.; Sinclair, L.V.; Feijoo, C.; Waugh, C.M.; Hagenbeek, T.J.; Spits, H.; Cantrell, D.A. Phosphoinositide-dependent kinase 1 con-trols migration and malignant transformation but not cell growth and proliferation in PTEN-null lymphocytes. J. Exp. Med., 2009, 206(11), 2441-2454.
[http://dx.doi.org/10.1084/jem.20090219] [PMID: 19808258]
[67]
Delgoffe, G.M.; Woo, S.R.; Turnis, M.E.; Gravano, D.M.; Guy, C.; Overacre, A.E.; Bettini, M.L.; Vogel, P.; Finkelstein, D.; Bonnevier, J.; Workman, C.J.; Vignali, D.A. Stability and function of regulatory T cells is maintained by a neuropilin-1-semaphorin-4a axis. Nature, 2013, 501(7466), 252-256.
[http://dx.doi.org/10.1038/nature12428] [PMID: 23913274]
[68]
Michalek, R.D.; Gerriets, V.A.; Nichols, A.G.; Inoue, M.; Kazmin, D.; Chang, C.Y.; Dwyer, M.A.; Nelson, E.R.; Pollizzi, K.N.; Ilkayeva, O.; Giguere, V.; Zuercher, W.J.; Powell, J.D.; Shinohara, M.L.; McDonnell, D.P.; Rathmell, J.C. Estrogen-related receptor-α is a metabolic regulator of effector T-cell activation and differentiation. Proc. Natl. Acad. Sci. USA, 2011, 108(45), 18348-18353.
[http://dx.doi.org/10.1073/pnas.1108856108] [PMID: 22042850]
[69]
Klysz, D.; Tai, X.; Robert, P.A.; Craveiro, M.; Cretenet, G.; Oburoglu, L.; Mongellaz, C.; Floess, S.; Fritz, V.; Matias, M.I.; Yong, C.; Surh, N.; Marie, J.C.; Huehn, J.; Zimmermann, V.; Kinet, S.; Dardalhon, V.; Taylor, N. Glutamine-dependent α-ketoglutarate production regu-lates the balance between T helper 1 cell and regulatory T cell generation. Sci. Signal., 2015, 8(396), ra97.
[http://dx.doi.org/10.1126/scisignal.aab2610] [PMID: 26420908]
[70]
Bertout, J.A.; Patel, S.A.; Simon, M.C. The impact of O2 availability on human cancer. Nat. Rev. Cancer, 2008, 8(12), 967-975.
[http://dx.doi.org/10.1038/nrc2540] [PMID: 18987634]
[71]
Cheng, S-C.; Quintin, J.; Cramer, R.A.; Shepardson, K.M.; Saeed, S.; Kumar, V.; Giamarellos-Bourboulis, E.J.; Martens, J.H.; Rao, N.A.; Aghajanirefah, A. mTOR-and HIF-1α–mediated aerobic glycolysis as metabolic basis for trained immunity. Science, 2014, 345(6204), 1250684.
[72]
Semenza, G.L. Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer, 2003, 3(10), 721-732.
[http://dx.doi.org/10.1038/nrc1187] [PMID: 13130303]
[73]
Imtiyaz, H.Z.; Simon, M.C. Hypoxia-inducible factors as essential regulators of inflammation. Diverse Effects of Hypoxia on Tumor Pro-gression ; Springer; , 2010, pp. pp. 105-120.
[74]
Shi, L.Z.; Wang, R.; Huang, G.; Vogel, P.; Neale, G.; Green, D.R.; Chi, H. HIF1α-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J. Exp. Med., 2011, 208(7), 1367-1376.
[http://dx.doi.org/10.1084/jem.20110278] [PMID: 21708926]
[75]
Dang, C.V. Glutaminolysis: supplying carbon or nitrogen or both for cancer cells? Cell Cycle, 2010, 9(19), 3884-3886.
[http://dx.doi.org/10.4161/cc.9.19.13302] [PMID: 20948290]
[76]
Barsoum, I. B.; Smallwood, C. A.; Siemens, D. R.; Graham, C. H. A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells. Cancer Res., 2013.
[77]
Firth, J.D.; Ebert, B.L.; Pugh, C.W.; Ratcliffe, P.J. Oxygen-regulated control elements in the phosphoglycerate kinase 1 and lactate dehydrogenase A gene: similarities with the erythropoietin 3′ enhancer. Proc. Natl. Acad. Sci. USA, 1994, 91(14), 6496-6500.
[78]
Kim, J.W.; Tchernyshyov, I.; Semenza, G.L.; Dang, C.V. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab., 2006, 3(3), 177-185.
[http://dx.doi.org/10.1016/j.cmet.2006.02.002] [PMID: 16517405]
[79]
Neumann, A.K.; Yang, J.; Biju, M.P.; Joseph, S.K.; Johnson, R.S.; Haase, V.H.; Freedman, B.D.; Turka, L.A. Hypoxia inducible factor 1 alpha regulates T cell receptor signal transduction. Proc. Natl. Acad. Sci. USA, 2005, 102(47), 17071-17076.
[http://dx.doi.org/10.1073/pnas.0506070102] [PMID: 16286658]
[80]
Bell, E.L.; Klimova, T.A.; Eisenbart, J.; Moraes, C.T.; Murphy, M.P.; Budinger, G.R.; Chandel, N.S. The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production. J. Cell Biol., 2007, 177(6), 1029-1036.
[http://dx.doi.org/10.1083/jcb.200609074] [PMID: 17562787]
[81]
Kesarwani, P.; Murali, A. K.; Al-Khami, A. A.; Mehrotra, S. Redox regulation of T-cell function: from molecular mechanisms to significance in human health and disease. Antioxid. Redox. Signal., 2013, 18(12), 1497-1534.
[82]
Doedens, A.L.; Phan, A.T.; Stradner, M.H.; Fujimoto, J.K.; Nguyen, J.V.; Yang, E.; Johnson, R.S.; Goldrath, A.W. Hypoxia-inducible factors enhance the effector responses of CD8(+) T cells to persistent antigen. Nat. Immunol., 2013, 14(11), 1173-1182.
[http://dx.doi.org/10.1038/ni.2714] [PMID: 24076634]
[83]
Finlay, D.K.; Rosenzweig, E.; Sinclair, L.V.; Feijoo-Carnero, C.; Hukelmann, J.L.; Rolf, J.; Panteleyev, A.A.; Okkenhaug, K.; Cantrell, D.A. PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells. J. Exp. Med., 2012, 209(13), 2441-2453.
[http://dx.doi.org/10.1084/jem.20112607] [PMID: 23183047]
[84]
Tang, Y.A.; Chen, Y.F.; Bao, Y.; Mahara, S.; Yatim, S.M.J.; Oguz, G.; Lee, P.L.; Feng, M.; Cai, Y.; Tan, E.Y.; Fong, S.S. Hypoxic tumor microenvironment activates GLI2 via HIF-1α and TGF-β2 to promote chemoresistance in colorectal cancer. Proc. Natl. Acad. Sci., 2018, 115(26), E5990-E5999.
[85]
Klaus, A.; Fathi, O.; Tatjana, T.-W.; Bruno, N.; Oskar, K. J. P.; Research, O. Expression of hypoxia-associated protein HIF-1α in follicular thyroid cancer is associated with distant metastasis. Pathol. Oncol. Res., 2018, 24(2), 289-296.
[86]
Fang, H.Y.; Hughes, R.; Murdoch, C.; Coffelt, S.B.; Biswas, S.K.; Harris, A.L.; Johnson, R.S.; Imityaz, H.Z.; Simon, M.C.; Fredlund, E.; Greten, F.R.; Rius, J.; Lewis, C.E. Hypoxia-inducible factors 1 and 2 are important transcriptional effectors in primary macrophages expe-riencing hypoxia. Blood, 2009, 114(4), 844-859.
[http://dx.doi.org/10.1182/blood-2008-12-195941] [PMID: 19454749]
[87]
Nizet, V.; Johnson, R.S. Interdependence of hypoxic and innate immune responses. Nat. Rev. Immunol., 2009, 9(9), 609-617.
[http://dx.doi.org/10.1038/nri2607] [PMID: 19704417]
[88]
Semenza, G.L. HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J. Clin. Invest., 2013, 123(9), 3664-3671.
[http://dx.doi.org/10.1172/JCI67230] [PMID: 23999440]
[89]
Clambey, E.T.; McNamee, E.N.; Westrich, J.A.; Glover, L.E.; Campbell, E.L.; Jedlicka, P.; de Zoeten, E.F.; Cambier, J.C.; Stenmark, K.R.; Colgan, S.P.; Eltzschig, H.K. Hypoxia-inducible factor-1 alpha-dependent induction of FoxP3 drives regulatory T-cell abundance and function during inflammatory hypoxia of the mucosa. Proc. Natl. Acad. Sci. USA, 2012, 109(41), E2784-E2793.
[http://dx.doi.org/10.1073/pnas.1202366109] [PMID: 22988108]
[90]
Facciabene, A.; Motz, G.T.; Coukos, G. T-regulatory cells: key players in tumor immune escape and angiogenesis. Cancer Res., 2012, 72(9), 2162-2171.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-3687] [PMID: 22549946]
[91]
Roman, J.; Ritzenthaler, J.D.; Roser-Page, S.; Sun, X.; Han, S. alpha5beta1-integrin expression is essential for tumor progression in exper-imental lung cancer. Am. J. Respir. Cell Mol. Biol., 2010, 43(6), 684-691.
[http://dx.doi.org/10.1165/rcmb.2009-0375OC] [PMID: 20081050]
[92]
Makino, Y.; Nakamura, H.; Ikeda, E.; Ohnuma, K.; Yamauchi, K.; Yabe, Y.; Poellinger, L.; Okada, Y.; Morimoto, C.; Tanaka, H. Hypoxia-inducible factor regulates survival of antigen receptor-driven T cells. J. immunol., 2003, 171(12), 6534-6540.
[93]
Laplante, M.; Sabatini, D.M. mTOR signaling in growth control and disease. Cell, 2012, 149(2), 274-293.
[http://dx.doi.org/10.1016/j.cell.2012.03.017] [PMID: 22500797]
[94]
Siska, P.J.; Rathmell, J.C. T cell metabolic fitness in anti-tumor immunity. Trends Immunol., 2015, 36(4), 257-264.
[http://dx.doi.org/10.1016/j.it.2015.02.007] [PMID: 25773310]
[95]
Rao, R.R.; Li, Q.; Odunsi, K.; Shrikant, P.A. The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating the expression of transcription factors T-bet and Eomesodermin. Immunity, 2010, 32(1), 67-78.
[http://dx.doi.org/10.1016/j.immuni.2009.10.010] [PMID: 20060330]
[96]
Chen, L.; Flies, D.B. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat. Rev. Immunol., 2013, 13(4), 227-242.
[http://dx.doi.org/10.1038/nri3405] [PMID: 23470321]
[97]
Dan, H.C.; Ebbs, A.; Pasparakis, M.; Van Dyke, T.; Basseres, D.S.; Baldwin, A.S. Akt-dependent activation of mTORC1 complex involves phosphorylation of mTOR (mammalian target of rapamycin) by IκB kinase α (IKKα). J. Biol. Chem., 2014, 289(36), 25227-25240.
[http://dx.doi.org/10.1074/jbc.M114.554881] [PMID: 24990947]
[98]
Morita, M.; Gravel, S.P.; Hulea, L.; Larsson, O.; Pollak, M.; St-Pierre, J.; Topisirovic, I. mTOR coordinates protein synthesis, mitochon-drial activity and proliferation. Cell Cycle, 2015, 14(4), 473-480.
[http://dx.doi.org/10.4161/15384101.2014.991572] [PMID: 25590164]
[99]
Delgoffe, G.M.; Powell, J.D. mTOR: taking cues from the immune microenvironment. Immunology, 2009, 127(4), 459-465.
[http://dx.doi.org/10.1111/j.1365-2567.2009.03125.x] [PMID: 19604300]
[100]
Zheng, Y.; Collins, S. L.; Lutz, M. A.; Allen, A. N.; Kole, T. P.; Zarek, P. E.; Powell, J. D. A role for mammalian target of rapamycin in regulating T cell activation versus energy. J. Immunol., (Baltimore, Md.: 1950), 2007, 178(4), 2163-2170.
[101]
Delgoffe, G.M.; Kole, T.P.; Zheng, Y.; Zarek, P.E.; Matthews, K.L.; Xiao, B.; Worley, P.F.; Kozma, S.C.; Powell, J.D. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity, 2009, 30(6), 832-844.
[http://dx.doi.org/10.1016/j.immuni.2009.04.014]
[102]
Yang, K.; Shrestha, S.; Zeng, H.; Karmaus, P.W.; Neale, G.; Vogel, P.; Guertin, D.A.; Lamb, R.F.; Chi, H. T cell exit from qui-escence and differentiation into Th2 cells depend on Raptor-mTORC1-mediated metabolic reprogramming. Immunity, 2013, 39(6), 1043-1056.
[http://dx.doi.org/10.1016/j.immuni.2013.09.015]
[103]
Li, M.O.; Rudensky, A.Y. T cell receptor signalling in the control of regulatory T cell differentiation and function. 2016, 16(4), 220-223.
[104]
Neama, A.F.; Looi, C.Y.; Wong, W.F. Autoimmunity; infection, multiple players in the mechanical control of t cell quiescence, Cancer, Autoimmun. Infection, 2017, 97.
[105]
Zhang, L.; Romero, P. Metabolic control of CD8+ T cell fate decisions and anti-tumor immunity. Trends Mol. Med., 2018, 24(1), 30-48.
[106]
Finlay, D.; Cantrell, D. Phosphoinositide 3-kinase and the mammalian target of rapamycin pathways control T cell migration. 2010, 1183(1), 149-157.
[107]
Liu, Y.; Zhang, D.T.; Liu, X.G. mTOR signaling in T cell immunity and autoimmunity. Int. Rev. Immunol., 2015, 34(1), 50-66.
[108]
Powell, J.D.; Pollizzi, K.N.; Heikamp, E.B.; Horton, M.R. Regulation of immune responses by mTOR. Annu. Rev. Immunol., 2012, 30, 39-68.
[http://dx.doi.org/10.1146/annurev-immunol-020711-075024]
[109]
Colina, R.; Costa-Mattioli, M.; Dowling, R.J.; Jaramillo, M.; Tai, L.H.; Breitbach, C.J.; Martineau, Y.; Larsson, O.; Rong, L.; Svitkin, Y.V.; Makrigiannis, A.P. Translational control of the innate immune response through IRF-7. Nature, 2008, 452(7185), 323.
[http://dx.doi.org/10.1038/nature06730]
[110]
Venturi, V.; Masek, T.; Pospisek, M. A blood pact: the significance and implications of eif4e on lymphocytic leukemia. 2018, 67(3), 363-382.
[111]
Sinclair, L.V.; Rolf, J.; Emslie, E.; Shi, Y.B.; Taylor, P.M.; Cantrell, D.A. Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation. 2013, 14(5), 500.
[112]
Nakaya, M.; Xiao, Y.; Zhou, X.; Chang, J.H.; Chang, M.; Cheng, X.; Blonska, M.; Lin, X.; Sun, S.C. Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation. 2014, 40(5), 692-705.
[113]
Rao, R.R.; Li, Q.; Gubbels Bupp, M.R.; Shrikant, P.A. Transcription factor Foxo1 represses T-bet-mediated effector functions and pro-motes memory CD8(+) T cell differentiation. Immunity, 2012, 36(3), 374-387.
[PMID: 22425248] [http://dx.doi.org/10.1016/j.immuni.2012.01.015]
[114]
Ouyang, W.; Beckett, O.; Ma, Q.; Paik, J.H.; DePinho, R.A.; Li, M.O. Foxo proteins cooperatively control the differentiation of Foxp3+ regulatory T cells. Nat. Immunol., 2010, 11(7), 618-627.
[http://dx.doi.org/10.1038/ni.1884] [PMID: 20467422]
[115]
Ruf, M.; Moch, H.; Schraml, P. PD-L1 expression is regulated by hypoxia inducible factor in clear cell renal cell carcinoma. Int. J. Cancer, 2016, 139(2), 396-403.
[http://dx.doi.org/10.1002/ijc.30077] [PMID: 26945902]
[116]
Patsoukis, N.; Bardhan, K.; Chatterjee, P.; Sari, D.; Liu, B.; Bell, L.N.; Karoly, E.D.; Freeman, G.J.; Petkova, V.; Seth, P.; Li, L.; Boussio-tis, V.A. PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nat. Commun., 2015, 6, 6692.
[http://dx.doi.org/10.1038/ncomms7692] [PMID: 25809635]
[117]
O’Sullivan, D.; Pearce, E.L. Targeting T cell metabolism for therapy. Trends Immunol., 2015, 36(2), 71-80.
[http://dx.doi.org/10.1016/j.it.2014.12.004] [PMID: 25601541]
[118]
Villadolid, J.; Amin, A. Immune checkpoint inhibitors in clinical practice: update on management of immune-related toxicities. Transl. Lung Cancer Res., 2015, 4(5), 560-575.
[PMID: 26629425]
[119]
Zhao, Z.; Zhang, X.; Su, L.; Xu, L.; Zheng, Y.; Sun, J. Fine tuning subsets of CD4+ T cells by low-dosage of IL-2 and a new therapeutic strategy for autoimmune diseases. Int. Immunopharmacol., 2018, 56, 269-276.
[120]
Myers, D.R.; Wheeler, B.; Roose, J.P. mTOR and other effector kinase signals that impact T cell function and activity. 2019, 291(1), 134-153.
[121]
Lee, C-F.; Lo, Y-C.; Cheng, C-H.; Furtmüller, G.J.; Oh, B.; Andrade-Oliveira, V.; Thomas, A.G.; Bowman, C.E.; Slusher, B.S.; Wolf-gang, M.J.J.C.r. Preventing allograft rejection by targeting immune metabolism. Immunol. Rev., 2015, 13(4), 760-770.
[http://dx.doi.org/10.1016/j.celrep.2015.09.036]
[122]
Berod, L.; Friedrich, C.; Nandan, A.; Freitag, J.; Hagemann, S.; Harmrolfs, K.; Sandouk, A.; Hesse, C.; Castro, C.N.; Bähre, H.; Tschirner, S.K. De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat. Med., 2014, 20(11), 1327-1333.
[http://dx.doi.org/10.1038/nm.3704]
[123]
Shi, L.Z.; Wang, R.; Huang, G.; Vogel, P.; Neale, G.; Green, D.R.; Chi, H. HIF1α–dependent glycolytic pathway orches-trates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J. Exp. Med., 2011, 208(7), 1367-1376.
[124]
Sharma, M.D.; Shinde, R.; McGaha, T.L.; Huang, L.; Holmgaard, R.B.; Wolchok, J.D.; Mautino, M.R.; Celis, E.; Sharpe, A.H.; Francisco, L.M.; Powell, J.D. The PTEN pathway in Tregs is a critical driver of the suppressive tumor microenvironment. Sci. Adv., 2015, 1(10), e1500845.
[http://dx.doi.org/10.1126/sciadv.1500845]
[125]
Schurich, A.; Magalhaes, I.; Mattsson, J. Metabolic regulation of CAR T cell function by the hypoxic microenvironment in sol-id tumors. Immunotherapy, 2019, 11(4), 335-345.
[http://dx.doi.org/10.2217/imt-2018-0141]
[126]
Greiner, E.F.; Guppy, M.; Brand, K. Glucose is essential for proliferation and the glycolytic enzyme induction that provokes a transition to glycolytic energy production. J. Biol. Chem., 1994, 269(50), 31484-31490.
[127]
Carr, E.L.; Kelman, A.; Wu, G.S.; Gopaul, R.; Senkevitch, E.; Aghvanyan, A.; Turay, A.M.; Frauwirth, K.A. Glutamine uptake and metabolism are coordinately regulated by ERK/MAPK during T lymphocyte activation. J. Immunol., 2010, 0903586.
[128]
Wofford, J.A.; Wieman, H.L.; Jacobs, S.R.; Zhao, Y.; Rathmell, J.C. IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival. Blood, 2008, 111(4), 2101-2111.
[129]
Blagih, J.; Coulombe, F.; Vincent, E.E.; Dupuy, F.; Galicia-Vázquez, G.; Yurchenko, E.; Raissi, T.C.; van der Windt, G.J.; Viollet, B.; Pearce, E.L.; Pelletier, J. The energy sensor AMPK regulates T cell metabolic adaptation and effector responses in vivo. Immunity, 2015, 42(1), 41-54.
[http://dx.doi.org/10.1016/j.immuni.2014.12.030]
[130]
Sommershof, A.; Scheuermann, L.; Koerner, J.; Groettrup, M. Behavior, immunity, Chronic stress suppresses anti-tumor TCD8+ responses and tumor regression following cancer immunotherapy in a mouse model of melanoma. Brain Behav. Immun., 2017, 65, 140-149.
[131]
Chang, C-H.; Qiu, J.; O’Sullivan, D.; Buck, M.D.; Noguchi, T.; Curtis, J.D.; Chen, Q.; Gindin, M.; Gubin, M.M.; van der Windt, G.J.; Tonc, E.; Schreiber, R.D.; Pearce, E.J.; Pearce, E.L. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell, 2015, 162(6), 1229-1241.
[http://dx.doi.org/10.1016/j.cell.2015.08.016] [PMID: 26321679]
[132]
Fischer, K.; Hoffmann, P.; Voelkl, S.; Meidenbauer, N.; Ammer, J.; Edinger, M.; Gottfried, E.; Schwarz, S.; Rothe, G.; Hoves, S.; Renner, K.; Timischl, B.; Mackensen, A.; Kunz-Schughart, L.; Andreesen, R.; Krause, S.W.; Kreutz, M. Inhibitory effect of tumor cell-derived lac-tic acid on human T cells. Blood, 2007, 109(9), 3812-3819.
[http://dx.doi.org/10.1182/blood-2006-07-035972] [PMID: 17255361]
[133]
Ogura, A.; Akiyoshi, T.; Yamamoto, N.; Kawachi, H.; Ishikawa, Y.; Mori, S.; Oba, K.; Nagino, M.; Fukunaga, Y.; Ueno, M. Pattern of programmed cell death-ligand 1 expression and CD8-positive T-cell infiltration before and after chemoradiotherapy in rectal cancer. Eur. J. Cancer, 2018, 91, 11-20.
[http://dx.doi.org/10.1016/j.ejca.2017.12.005]
[134]
Maciver, N.J.; Jacobs, S.R.; Wieman, H.L.; Wofford, J.A.; Coloff, J.L.; Rathmell, J.C. Glucose metabolism in lymphocytes is a regulated process with significant effects on immune cell function and survival. J. Leukoc. Biol., 2008, 84(4), 949-957.
[http://dx.doi.org/10.1189/jlb.0108024] [PMID: 18577716]
[135]
Osborn, J.F.; Hobbs, S.J.; Mooster, J.L.; Khan, T.N.; Kilgore, A.M.; Harbour, J.C.; Nolz, J. Central memory CD8+ T cells become CD69+ tissue-residents during viral skin infection independent of CD62L-mediated lymph node surveillance. PLoS Pathog., 2019, 15(3), e1007633.
[136]
Dang, E.V.; Barbi, J.; Yang, H-Y.; Jinasena, D.; Yu, H.; Zheng, Y.; Bordman, Z.; Fu, J.; Kim, Y.; Yen, H-R.; Luo, W.; Zeller, K.; Shimoda, L.; Topalian, S.L.; Semenza, G.L.; Dang, C.V.; Pardoll, D.M.; Pan, F. Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell, 2011, 146(5), 772-784.
[http://dx.doi.org/10.1016/j.cell.2011.07.033] [PMID: 21871655]
[137]
Magg, T.; Wiebking, V.; Conca, R.; Krebs, S.; Arens, S.; Schmid, I.; Klein, C.; Albert, M.H.; Hauck, F. IPEX due to an ex-on 7 skipping FOXP3 mutation with autoimmune diabetes mellitus cured by selective TReg cell engraftment. Clin. Immunol., 2018, 191, 52-58.
[138]
Gallaher, Z.R.; Steward, O. Modest enhancement of sensory axon regeneration in the sciatic nerve with conditional co-deletion of PTEN and SOCS3 in the dorsal root ganglia of adult mice. Exp. Neurol., 2018, 303, 120-133.
[http://dx.doi.org/10.1016/j.expneurol.2018.02.012]
[139]
Qin, H.; Wang, L.; Feng, T.; Elson, C.O.; Niyongere, S.A.; Lee, S.J.; Reynolds, S.L.; Weaver, C.T.; Roarty, K.; Serra, R. TGF-β pro-motes Th17 cell development through inhibition of SOCS3. J. Immunol., 2009, 0801986.
[140]
Wei, X.; Ai, K.; Li, H.; Zhang, Y.; Li, K.; Yang, J. Ancestral T cells in fish require mTORC1-coupled immune signals and metabolic programming for proper activation and function. J. Immunol., 2019, 203(5), 1172-1188.
[http://dx.doi.org/10.4049/jimmunol.1900008]
[141]
Sugiura, A.; Rathmell, J.C. Metabolic barriers to T cell function in tumors. J. Immunol., 2018, 200(2), 400-407.
[http://dx.doi.org/10.4049/jimmunol.1701041] [PMID: 29311381]
[142]
Andrejeva, G.; Rathmell, J.C. Similarities and distinctions of cancer and immune metabolism in inflammation and tumors. Cell Metab., 2017, 26(1), 49-70.
[http://dx.doi.org/10.1016/j.cmet.2017.06.004] [PMID: 28683294]
[143]
Wang, R.; Dillon, C.P.; Shi, L.Z.; Milasta, S.; Carter, R.; Finkelstein, D.; McCormick, L.L.; Fitzgerald, P.; Chi, H.; Munger, J.; Green, D.R. The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity, 2011, 35(6), 871-882.
[http://dx.doi.org/10.1016/j.immuni.2011.09.021] [PMID: 22195744]
[144]
Riha, P.; Rudd, C.E. CD28 co-signaling in the adaptive immune response. Self Nonself, 2010, 1(3), 231-240.
[http://dx.doi.org/10.4161/self.1.3.12968] [PMID: 21487479]
[145]
Jacobs, S.R.; Herman, C.E.; Maciver, N.J.; Wofford, J.A.; Wieman, H.L.; Hammen, J.J.; Rathmell, J.C. Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways. J. Immunol., 2008, 180(7), 4476-4486.
[http://dx.doi.org/10.4049/jimmunol.180.7.4476] [PMID: 18354169]
[146]
Carr, E.L.; Kelman, A.; Wu, G.S.; Gopaul, R.; Senkevitch, E.; Aghvanyan, A.; Turay, A.M.; Frauwirth, K.A. Glutamine uptake and me-tabolism are coordinately regulated by ERK/MAPK during T lymphocyte activation. J. Immunol., 2010, 185(2), 1037-1044.
[http://dx.doi.org/10.4049/jimmunol.0903586] [PMID: 20554958]
[147]
Palmer, C.S.; Hussain, T.; Duette, G.; Weller, T.J.; Ostrowski, M.; Sada-Ovalle, I.; Crowe, S.M. Regulators of glucose metabolism in CD4+ and CD8+ T Cells. Int. Rev. Immunol., 2016, 35(6), 477-488.
[http://dx.doi.org/10.3109/08830185.2015.1082178] [PMID: 26606199]
[148]
Chou, C.; Pinto, A.K.; Curtis, J.D.; Persaud, S.P.; Cella, M.; Lin, C-C.; Edelson, B.T.; Allen, P.M.; Colonna, M.; Pearce, E.L.; Diamond, M.S.; Egawa, T. c-Myc-induced transcription factor AP4 is required for host protection mediated by CD8+ T cells. Nat. Immunol., 2014, 15(9), 884-893.
[http://dx.doi.org/10.1038/ni.2943] [PMID: 25029552]
[149]
Papandreou, I.; Cairns, R.A.; Fontana, L.; Lim, A.L.; Denko, N.C. HIF-1 mediates adaptation to hypoxia by actively downregulating mito-chondrial oxygen consumption. Cell Metab., 2006, 3(3), 187-197.
[http://dx.doi.org/10.1016/j.cmet.2006.01.012] [PMID: 16517406]
[150]
Vander Heiden, M.G.; DeBerardinis, R.J. Understanding the intersections between metabolism and cancer biology. Cell, 2017, 168(4), 657-669.
[http://dx.doi.org/10.1016/j.cell.2016.12.039] [PMID: 28187287]
[151]
Wojdylo, J. Metabolism of CD4+ Th1 and Th2 cells.,
[152]
Zheng, Y.; Delgoffe, G. M.; Meyer, C. F.; Chan, W.; Powell, J. D. Anergic T cells are metabolically anergic. J. Immunol. (Baltimore, Md.:1950), 2009, 183(10), 6095-6101.
[153]
Delgoffe, G.M.; Kole, T.P.; Zheng, Y.; Zarek, P.E.; Matthews, K.L.; Xiao, B.; Worley, P.F.; Kozma, S.C.; Powell, J.D. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity, 2009, 30(6), 832-844.
[http://dx.doi.org/10.1016/j.immuni.2009.04.014] [PMID: 19538929]
[154]
Gerriets, V.A. Glucose Metabolism in CD4+ T cell Subsets Modulates Inflammation and Autoimmunity ; (Doctoral dissertation) Duke University, 2014.
[155]
Waickman, A.T.; Powell, J.D. mTOR, metabolism, and the regulation of T-cell differentiation and function. Immunol. Rev., 2012, 249(1), 43-58.
[http://dx.doi.org/10.1111/j.1600-065X.2012.01152.x] [PMID: 22889214]
[156]
Delgoffe, G.M.; Pollizzi, K.N.; Waickman, A.T.; Heikamp, E.; Meyers, D.J.; Horton, M.R.; Xiao, B.; Worley, P.F.; Powell, J.D. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat. Immunol., 2011, 12(4), 295-303.
[http://dx.doi.org/10.1038/ni.2005] [PMID: 21358638]
[157]
Cui, G.; Qin, X.; Wu, L.; Zhang, Y.; Sheng, X.; Yu, Q.; Sheng, H.; Xi, B.; Zhang, J.Z.; Zang, Y.Q. Liver X receptor (LXR) mediates nega-tive regulation of mouse and human Th17 differentiation. J. Clin. Invest., 2011, 121(2), 658-670.
[http://dx.doi.org/10.1172/JCI42974] [PMID: 21266776]
[158]
Zeng, H.; Yang, K.; Cloer, C.; Neale, G.; Vogel, P.; Chi, H. mTORC1 couple’s immune signals and metabolic programming to establish T(reg)-cell function. Nature, 2013, 499(7459), 485-490.
[http://dx.doi.org/10.1038/nature12297] [PMID: 23812589]
[159]
Ho, P-C.; Bihuniak, J.D.; Macintyre, A.N.; Staron, M.; Liu, X.; Amezquita, R.; Tsui, Y-C.; Cui, G.; Micevic, G.; Perales, J.C.; Kleinstein, S.H.; Abel, E.D.; Insogna, K.L.; Feske, S.; Locasale, J.W.; Bosenberg, M.W.; Rathmell, J.C.; Kaech, S.M. Phosphoenolpyruvate is a meta-bolic checkpoint of anti-tumor T cell responses. Cell, 2015, 162(6), 1217-1228.
[http://dx.doi.org/10.1016/j.cell.2015.08.012] [PMID: 26321681]
[160]
Lee, C-F.; Lo, Y-C.; Cheng, C-H.; Furtmüller, G.J.; Oh, B.; Andrade-Oliveira, V.; Thomas, A.G.; Bowman, C.E.; Slusher, B.S.; Wolfgang, M.J.; Brandacher, G.; Powell, J.D. Preventing allograft rejection by targeting immune metabolism. Cell Rep., 2015, 13(4), 760-770.
[http://dx.doi.org/10.1016/j.celrep.2015.09.036] [PMID: 26489460]
[161]
Dumitru, C.; Kabat, A.; Maloy, K. Metabolic adaptations of CD4+ T cells in inflammatory disease. Front. Immunol., 2018, 15(9), 540.
[162]
Mezrich, J.D.; Fechner, J.H.; Zhang, X.; Johnson, B.P.; Burlingham, W.J.; Bradfield, C.A. An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J. Immunol., 2010, 185(6), 3190-3198.
[http://dx.doi.org/10.4049/jimmunol.0903670] [PMID: 20720200]
[163]
Opitz, C.A.; Litzenburger, U.M.; Sahm, F.; Ott, M.; Tritschler, I.; Trump, S.; Schumacher, T.; Jestaedt, L.; Schrenk, D.; Weller, M.; Jugold, M.; Guillemin, G.J.; Miller, C.L.; Lutz, C.; Radlwimmer, B.; Lehmann, I.; von Deimling, A.; Wick, W.; Platten, M. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature, 2011, 478(7368), 197-203.
[http://dx.doi.org/10.1038/nature10491] [PMID: 21976023]
[164]
van der Windt, G.J.; Everts, B.; Chang, C-H.; Curtis, J.D.; Freitas, T.C.; Amiel, E.; Pearce, E.J.; Pearce, E.L. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity, 2012, 36(1), 68-78.
[http://dx.doi.org/10.1016/j.immuni.2011.12.007] [PMID: 22206904]
[165]
Cui, G.; Staron, M.M.; Gray, S.M.; Ho, P-C.; Amezquita, R.A.; Wu, J.; Kaech, S.M. IL-7-induced glycerol transport and TAG synthesis promotes memory CD8+ T cell longevity. Cell, 2015, 161(4), 750-761.
[http://dx.doi.org/10.1016/j.cell.2015.03.021] [PMID: 25957683]
[166]
O’Sullivan, D.; van der Windt, G.J.; Huang, S.C-C.; Curtis, J.D.; Chang, C-H.; Buck, M.D.; Qiu, J.; Smith, A.M.; Lam, W.Y.; DiPlato, L.M.; Hsu, F.F.; Birnbaum, M.J.; Pearce, E.J.; Pearce, E.L. Memory CD8(+) T cells use cell-intrinsic lipolysis to support the metabolic pro-gramming necessary for development. Immunity, 2014, 41(1), 75-88.
[http://dx.doi.org/10.1016/j.immuni.2014.06.005] [PMID: 25001241]
[167]
Cipolletta, D.; Feuerer, M.; Li, A.; Kamei, N.; Lee, J.; Shoelson, S.E.; Benoist, C.; Mathis, D. PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature, 2012, 486(7404), 549-553.
[http://dx.doi.org/10.1038/nature11132] [PMID: 22722857]
[168]
Burzyn, D.; Benoist, C.; Mathis, D. Regulatory T cells in nonlymphoid tissues. Nat. Immunol., 2013, 14(10), 1007-1013.
[http://dx.doi.org/10.1038/ni.2683] [PMID: 24048122]
[169]
Arpaia, N.; Campbell, C.; Fan, X.; Dikiy, S.; van der Veeken, J.; deRoos, P.; Liu, H.; Cross, J.R.; Pfeffer, K.; Coffer, P.J.; Rudensky, A.Y. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature, 2013, 504(7480), 451-455.
[http://dx.doi.org/10.1038/nature12726] [PMID: 24226773]
[170]
Smith, P.M.; Howitt, M.R.; Panikov, N.; Michaud, M.; Gallini, C.A.; Bohlooly-Y, M.; Glickman, J.N.; Garrett, W.S. The microbial metabo-lites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science, 2013, 341(6145), 569-573.
[http://dx.doi.org/10.1126/science.1241165] [PMID: 23828891]

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