Regulation of T cell immunity by cellular metabolism

doi:10.1007/s11684-018-0668-2

Frontiers of Medicine

2018, Vol. 12

Issue (4): 463-472 https://doi.org/10.1007/s11684-018-0668-2

本期目录

Regulation of T cell immunity by cellular metabolism

Zhilin Hu, Qiang Zou(

), Bing Su(

)

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

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Abstract：

T cells are an important adaptive immune response arm that mediates cell-mediated immunity. T cell metabolism plays a central role in T cell activation, proliferation, differentiation, and effector function. Specific metabolic programs are tightly controlled to mediate T cell immune responses, and alterations in T cell metabolism may result in many immunological disorders. In this review, we will summarize the main T cell metabolic pathways and the important factors participating in T cell metabolic programming during T cell homeostasis, differentiation, and function.

Key words： T cell immunity metabolic pathways nutrient uptake metabolic checkpoints

收稿日期: 2018-04-06 出版日期: 2018-09-03

Corresponding Author(s): Qiang Zou,Bing Su

引用本文:

. [J]. Frontiers of Medicine, 2018, 12(4): 463-472.
Zhilin Hu, Qiang Zou, Bing Su. Regulation of T cell immunity by cellular metabolism. Front. Med., 2018, 12(4): 463-472.

链接本文:

https://academic.hep.com.cn/fmd/CN/10.1007/s11684-018-0668-2
https://academic.hep.com.cn/fmd/CN/Y2018/V12/I4/463

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1	Segal BH. Role of macrophages in host defense against aspergillosis and strategies for immune augmentation. Oncologist 2007; 12(Suppl 2): 7–13 pmid: 18039634
2	Harwood CG, Rao RP. Host pathogen relations: exploring animal models for fungal pathogens. Pathogens 2014; 3(3): 549–562 https://doi.org/10.3390/pathogens3030549 pmid: 25438011
3	Ron-Harel N, Sharpe AH, Haigis MC. Mitochondrial metabolism in T cell activation and senescence: a mini-review. Gerontology 2015; 61(2): 131–138 https://doi.org/10.1159/000362502 pmid: 25402204
4	Pearce EL, Pearce EJ. Metabolic pathways in immune cell activation and quiescence. Immunity 2013; 38(4): 633–643 https://doi.org/10.1016/j.immuni.2013.04.005 pmid: 23601682
5	Pennock ND, White JT, Cross EW, Cheney EE, Tamburini BA, Kedl RM. T cell responses: naïve to memory and everything in between. Adv Physiol Educ 2013; 37(4): 273–283 https://doi.org/10.1152/advan.00066.2013 pmid: 24292902
6	Lauvau G, Soudja SM. Mechanisms of Memory T Cell Activation and Effective Immunity. Crossroads, between Innate and Adaptive Immunity. Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 850). 2015; 850: 73–80 https://doi.org/10.1007/978-3-319-15774-0_6 pmid: 26324347
7	Brenchley JM, Douek DC, Ambrozak DR, Chatterji M, Betts MR, Davis LS, Koup RA. Expansion of activated human naïve T-cells precedes effector function. Clin Exp Immunol 2002; 130(3): 432–440 https://doi.org/10.1046/j.1365-2249.2002.02015.x pmid: 12452833
8	Zhang N, Hartig H, Dzhagalov I, Draper D, He YW. The role of apoptosis in the development and function of T lymphocytes. Cell Res 2005; 15(10): 749–769 https://doi.org/10.1038/sj.cr.7290345 pmid: 16246265
9	Schumacher TN, Gerlach C, van Heijst JW. Mapping the life histories of T cells. Nat Rev Immunol 2010; 10(9): 621–631 https://doi.org/10.1038/nri2822 pmid: 20689559
10	Wang R, Green DR. Metabolic checkpoints in activated T cells. Nat Immunol 2012; 13(10): 907–915 https://doi.org/10.1038/ni.2386 pmid: 22990888
11	Ray JP, Staron MM, Shyer JA, Ho PC, Marshall HD, Gray SM, Laidlaw BJ, Araki K, Ahmed R, Kaech SM, Craft J. The interleukin-2-mTORc1 kinase axis defines the signaling, differentiation, and metabolism of T helper 1 and follicular B helper T cells. Immunity 2015; 43(4): 690–702 https://doi.org/10.1016/j.immuni.2015.08.017 pmid: 26410627
12	Wu T, Shin HM, Moseman EA, Ji Y, Huang B, Harly C, Sen JM, Berg LJ, Gattinoni L, McGavern DB, Schwartzberg PL. TCF1 is required for the T follicular helper cell response to viral infection. Cell Reports 2015; 12(12): 2099–2110 https://doi.org/10.1016/j.celrep.2015.08.049 pmid: 26365183
13	Johnston RJ, Poholek AC, DiToro D, Yusuf I, Eto D, Barnett B, Dent AL, Craft J, Crotty S. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 2009; 325(5943): 1006–1010 https://doi.org/10.1126/science.1175870 pmid: 19608860
14	Nurieva RI, Chung Y, Martinez GJ, Yang XO, Tanaka S, Matskevitch TD, Wang YH, Dong C. Bcl6 mediates the development of T follicular helper cells. Science 2009; 325(5943): 1001–1005 https://doi.org/10.1126/science.1176676 pmid: 19628815
15	Oestreich KJ, Read KA, Gilbertson SE, Hough KP, McDonald PW, Krishnamoorthy V, Weinmann AS. Bcl-6 directly represses the gene program of the glycolysis pathway. Nat Immunol 2014; 15(10): 957–964 https://doi.org/10.1038/ni.2985 pmid: 25194422
16	Oestreich KJ, Mohn SE, Weinmann AS. Molecular mechanisms that control the expression and activity of Bcl-6 in TH1 cells to regulate flexibility with a TFH-like gene profile. Nat Immunol 2012; 13(4): 405–411 https://doi.org/10.1038/ni.2242 pmid: 22406686
17	Scharping NE, Menk AV, Moreci RS, Whetstone RD, Dadey RE, Watkins SC, Ferris RL, Delgoffe GM. The tumor microenvironment represses T cell mitochondrial biogenesis to drive intratumoral T cell metabolic insufficiency and dysfunction. Immunity 2016; 45(3): 701–703 https://doi.org/10.1016/j.immuni.2016.08.009 pmid: 27653602
18	Bengsch B, Johnson AL, Kurachi M, Odorizzi PM, Pauken KE, Attanasio J, Stelekati E, McLane LM, Paley MA, Delgoffe GM, Wherry EJ. Bioenergetic insufficiencies due to metabolic alterations regulated by the inhibitory receptor PD-1 are an early driver of CD8+ T cell exhaustion. Immunity 2016; 45(2): 358–373 https://doi.org/10.1016/j.immuni.2016.07.008 pmid: 27496729
19	Austin S, St-Pierre J. PGC1a and mitochondrial metabolism—emerging concepts and relevance in ageing and neurodegenerative disorders. J Cell Sci 2012; 125(Pt 21): 4963–4971 https://doi.org/10.1242/jcs.113662 pmid: 23277535
20	Siska PJ, van der Windt GJ, Kishton RJ, Cohen S, Eisner W, MacIver NJ, Kater AP, Weinberg JB, Rathmell JC. Suppression of Glut1 and glucose metabolism by decreased Akt/mTORC1 signaling drives T cell impairment in B cell leukemia. J Immunol 2016; 197(6): 2532–2540 https://doi.org/10.4049/jimmunol.1502464 pmid: 27511728
21	Fox CJ, Hammerman PS, Thompson CB. Fuel feeds function: energy metabolism and the T-cell response. Nat Rev Immunol 2005; 5(11): 844–852 https://doi.org/10.1038/nri1710 pmid: 16239903
22	Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009; 324(5930): 1029–1033 https://doi.org/10.1126/science.1160809 pmid: 19460998
23	Wahl DR, Byersdorfer CA, Ferrara JL, Opipari AW Jr, Glick GD. Distinct metabolic programs in activated T cells: opportunities for selective immunomodulation. Immunol Rev 2012; 249(1): 104–115 https://doi.org/10.1111/j.1600-065X.2012.01148.x pmid: 22889218
24	De Boer RJ, Homann D, Perelson AS. Different dynamics of CD4+ and CD8+ T cell responses during and after acute lymphocytic choriomeningitis virus infection. J Immunol 2003; 171(8): 3928–3935 https://doi.org/10.4049/jimmunol.171.8.3928 pmid: 14530309
25	Pearce EL, Walsh MC, Cejas PJ, Harms GM, Shen H, Wang LS, Jones RG, Choi Y. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature 2009; 460(7251): 103–107 https://doi.org/10.1038/nature08097 pmid: 19494812
26	Schwenk RW, Holloway GP, Luiken JJ, Bonen A, Glatz JF. Fatty acid transport across the cell membrane: regulation by fatty acid transporters. Prostaglandins Leukot Essent Fatty Acids 2010; 82(4-6): 149–154 https://doi.org/10.1016/j.plefa.2010.02.029 pmid: 20206486
27	Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF, Sullivan SA, Nichols AG, Rathmell JC. 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 https://doi.org/10.4049/jimmunol.1003613 pmid: 21317389
28	Delgoffe GM, Pollizzi KN, Waickman AT, Heikamp E, Meyers DJ, Horton MR, Xiao B, Worley PF, Powell JD. 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 https://doi.org/10.1038/ni.2005 pmid: 21358638
29	van der Windt GJ, Everts B, Chang CH, Curtis JD, Freitas TC, Amiel E, Pearce EJ, Pearce EL. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity 2012; 36(1): 68–78 https://doi.org/10.1016/j.immuni.2011.12.007 pmid: 22206904
30	Lochner M, Berod L, Sparwasser T. Fatty acid metabolism in the regulation of T cell function. Trends Immunol 2015; 36(2): 81–91 https://doi.org/10.1016/j.it.2014.12.005 pmid: 25592731
31	Fraser KA, Schenkel JM, Jameson SC, Vezys V, Masopust D. Preexisting high frequencies of memory CD8+ T cells favor rapid memory differentiation and preservation of proliferative potential upon boosting. Immunity 2013; 39(1): 171–183 https://doi.org/10.1016/j.immuni.2013.07.003 pmid: 23890070
32	van der Windt GJ, O’Sullivan D, Everts B, Huang SC, Buck MD, Curtis JD, Chang CH, Smith AM, Ai T, Faubert B, Jones RG, Pearce EJ, Pearce EL. CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability. Proc Natl Acad Sci USA 2013; 110(35): 14336–14341 https://doi.org/10.1073/pnas.1221740110 pmid: 23940348
33	Nicholls DG. Spare respiratory capacity, oxidative stress and excitotoxicity. Biochem Soc Trans 2009; 37(Pt 6): 1385–1388 https://doi.org/10.1042/BST0371385 pmid: 19909281
34	Newsholme EA, Crabtree B, Ardawi MS. The role of high rates of glycolysis and glutamine utilization in rapidly dividing cells. Biosci Rep 1985; 5(5): 393–400 https://doi.org/10.1007/BF01116556 pmid: 3896338
35	van Stipdonk MJ, Hardenberg G, Bijker MS, Lemmens EE, Droin NM, Green DR, Schoenberger SP. Dynamic programming of CD8+ T lymphocyte responses. Nat Immunol 2003; 4(4): 361–365 https://doi.org/10.1038/ni912 pmid: 12640451
36	Rathmell JC, Vander Heiden MG, Harris MH, Frauwirth KA, Thompson CB. In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability. Mol Cell 2000; 6(3): 683–692 https://doi.org/10.1016/S1097-2765(00)00066-6 pmid: 11030347
37	Mueckler M, Thorens B. The SLC2 (GLUT) family of membrane transporters. Mol Aspects Med 2013; 34(2-3): 121–138 https://doi.org/10.1016/j.mam.2012.07.001 pmid: 23506862
38	Scheepers A, Joost HG, Schürmann A. The glucose transporter families SGLT and GLUT: molecular basis of normal and aberrant function. JPEN J Parenter Enteral Nutr 2004; 28(5): 364–371 https://doi.org/10.1177/0148607104028005364 pmid: 15449578
39	Wood IS, Trayhurn P. Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr 2003; 89(1): 3–9 https://doi.org/10.1079/BJN2002763 pmid: 12568659
40	Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC, Deoliveira D, Anderson SM, Abel ED, Chen BJ, Hale LP, Rathmell JC. The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab 2014; 20(1): 61–72 https://doi.org/10.1016/j.cmet.2014.05.004 pmid: 24930970
41	Qu Q, Zeng F, Liu X, Wang QJ, Deng F. Fatty acid oxidation and carnitine palmitoyltransferase I: emerging therapeutic targets in cancer. Cell Death Dis 2016; 7(5): e2226 https://doi.org/10.1038/cddis.2016.132 pmid: 27195673
42	Chakrabarti R, Jung CY, Lee TP, Liu H, Mookerjee BK. Changes in glucose transport and transporter isoforms during the activation of human peripheral blood lymphocytes by phytohemagglutinin. J Immunol 1994; 152(6): 2660–2668 pmid: 8144874
43	Frauwirth KA, Riley JL, Harris MH, Parry RV, Rathmell JC, Plas DR, Elstrom RL, June CH, Thompson CB. The CD28 signaling pathway regulates glucose metabolism. Immunity 2002; 16(6): 769–777 https://doi.org/10.1016/S1074-7613(02)00323-0 pmid: 12121659
44	Jacobs SR, Herman CE, Maciver NJ, Wofford JA, Wieman HL, Hammen JJ, Rathmell JC. Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways. J Immunol 2008; 180(7): 4476–4486 https://doi.org/10.4049/jimmunol.180.7.4476 pmid: 18354169
45	Nakaya M, Xiao Y, Zhou X, Chang JH, Chang M, Cheng X, Blonska M, Lin X, Sun SC. Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation. Immunity 2014; 40(5): 692–705 https://doi.org/10.1016/j.immuni.2014.04.007 pmid: 24792914
46	Sinclair LV, Rolf J, Emslie E, Shi YB, Taylor PM, Cantrell DA. Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation. Nat Immunol 2013; 14(5): 500–508 https://doi.org/10.1038/ni.2556 pmid: 23525088
47	Verrey F, Closs EI, Wagner CA, Palacin M, Endou H, Kanai Y. CATs and HATs: the SLC7 family of amino acid transporters. Pflugers Arch 2004; 447(5): 532–542 https://doi.org/10.1007/s00424-003-1086-z pmid: 14770310
48	Hayashi K, Jutabha P, Endou H, Sagara H, Anzai N. LAT1 is a critical transporter of essential amino acids for immune reactions in activated human T cells. J Immunol 2013; 191(8): 4080–4085 https://doi.org/10.4049/jimmunol.1300923 pmid: 24038088
49	Pearce EL, Walsh MC, Cejas PJ, Harms GM, Shen H, Wang LS, Jones RG, Choi Y. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature 2009; 460(7251): 103–107 https://doi.org/10.1038/nature08097 pmid: 19494812
50	Rao RR, Li Q, Odunsi K, Shrikant PA. 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 https://doi.org/10.1016/j.immuni.2009.10.010 pmid: 20060330
51	Araki K, Turner AP, Shaffer VO, Gangappa S, Keller SA, Bachmann MF, Larsen CP, Ahmed R. mTOR regulates memory CD8 T-cell differentiation. Nature 2009; 460(7251): 108–112 https://doi.org/10.1038/nature08155 pmid: 19543266
52	Brown EJ, Albers MW, Shin TB, Ichikawa K, Keith CT, Lane WS, Schreiber SL. A mammalian protein targeted by G1-arresting rapamycin-receptor complex. Nature 1994; 369(6483): 756–758 https://doi.org/10.1038/369756a0 pmid: 8008069
53	Delgoffe GM, Kole TP, Zheng Y, Zarek PE, Matthews KL, Xiao B, Worley PF, Kozma SC, Powell JD. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity 2009; 30(6): 832–844 https://doi.org/10.1016/j.immuni.2009.04.014 pmid: 19538929
54	Battaglia M, Stabilini A, Migliavacca B, Horejs-Hoeck J, Kaupper T, Roncarolo MG. Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J Immunol 2006; 177(12): 8338–8347 https://doi.org/10.4049/jimmunol.177.12.8338 pmid: 17142730
55	Battaglia M, Stabilini A, Roncarolo MG. Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood 2005; 105(12): 4743–4748 https://doi.org/10.1182/blood-2004-10-3932 pmid: 15746082
56	Kurebayashi Y, Nagai S, Ikejiri A, Ohtani M, Ichiyama K, Baba Y, Yamada T, Egami S, Hoshii T, Hirao A, Matsuda S, Koyasu S. PI3K-Akt-mTORC1-S6K1/2 axis controls Th17 differentiation by regulating Gfi1 expression and nuclear translocation of RORg. Cell Reports 2012; 1(4): 360–373 https://doi.org/10.1016/j.celrep.2012.02.007 pmid: 22832227
57	Wu X, Dou Y, Yang Y, Bian D, Luo J, Tong B, Xia Y, Dai Y. Arctigenin exerts anti-colitis efficacy through inhibiting the differentiation of Th1 and Th17 cells via an mTORC1-dependent pathway. Biochem Pharmacol 2015; 96(4): 323–336 https://doi.org/10.1016/j.bcp.2015.06.008 pmid: 26074264
58	Yang K, Shrestha S, Zeng H, Karmaus PW, Neale G, Vogel P, Guertin DA, Lamb RF, Chi H. T cell exit from quiescence and differentiation into Th2 cells depend on Raptor-mTORC1-mediated metabolic reprogramming. Immunity 2013; 39(6): 1043–1056 https://doi.org/10.1016/j.immuni.2013.09.015 pmid: 24315998
59	Lee K, Gudapati P, Dragovic S, Spencer C, Joyce S, Killeen N, Magnuson MA, Boothby M. Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity 2010; 32(6): 743–753 https://doi.org/10.1016/j.immuni.2010.06.002 pmid: 20620941
60	Buller CL, Loberg RD, Fan MH, Zhu Q, Park JL, Vesely E, Inoki K, Guan KL, Brosius FC 3rd. A GSK-3/TSC2/mTOR pathway regulates glucose uptake and GLUT1 glucose transporter expression. Am J Physiol Cell Physiol 2008; 295(3): C836–C843 https://doi.org/10.1152/ajpcell.00554.2007 pmid: 18650261
61	Gerriets VA, Kishton RJ, Nichols AG, Macintyre AN, Inoue M, Ilkayeva O, Winter PS, Liu X, Priyadharshini B, Slawinska ME, Haeberli L, Huck C, Turka LA, Wood KC, Hale LP, Smith PA, Schneider MA, MacIver NJ, Locasale JW, Newgard CB, Shinohara ML, Rathmell JC. Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation. J Clin Invest 2015; 125(1): 194–207 https://doi.org/10.1172/JCI76012 pmid: 25437876
62	Hadis U, Wahl B, Schulz O, Hardtke-Wolenski M, Schippers A, Wagner N, Müller W, Sparwasser T, Förster R, Pabst O. Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria. Immunity 2011; 34(2): 237–246 https://doi.org/10.1016/j.immuni.2011.01.016 pmid: 21333554
63	Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR, 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 https://doi.org/10.1084/jem.20110278 pmid: 21708926
64	Zeng H, Yang K, Cloer C, Neale G, Vogel P, Chi H. mTORC1 couples immune signals and metabolic programming to establish T(reg)-cell function. Nature 2013; 499(7459): 485–490 https://doi.org/10.1038/nature12297 pmid: 23812589
65	Hardie DG, Scott JW, Pan DA, Hudson ER. Management of cellular energy by the AMP-activated protein kinase system. FEBS Lett 2003; 546(1): 113–120 https://doi.org/10.1016/S0014-5793(03)00560-X pmid: 12829246
66	Hardie DG. Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status. Endocrinology 2003; 144(12): 5179–5183 https://doi.org/10.1210/en.2003-0982 pmid: 12960015
67	Tamás P, Hawley SA, Clarke RG, Mustard KJ, Green K, Hardie DG, Cantrell DA. Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca2+ in T lymphocytes. J Exp Med 2006; 203(7): 1665–1670 https://doi.org/10.1084/jem.20052469 pmid: 16818670
68	Xu J, Ji J, Yan XH. Cross-talk between AMPK and mTOR in regulating energy balance. Crit Rev Food Sci Nutr 2012; 52(5): 373–381 https://doi.org/10.1080/10408398.2010.500245 pmid: 22369257
69	Zhao D, Long XD, Lu TF, Wang T, Zhang WW, Liu YX, Cui XL, Dai HJ, Xue F, Xia Q. Metformin decreases IL-22 secretion to suppress tumor growth in an orthotopic mouse model of hepatocellular carcinoma. Int J Cancer 2015; 136(11): 2556–2565 https://doi.org/10.1002/ijc.29305 pmid: 25370454
70	Kang KY, Kim YK, Yi H, Kim J, Jung HR, Kim IJ, Cho JH, Park SH, Kim HY, Ju JH. Metformin downregulates Th17 cells differentiation and attenuates murine autoimmune arthritis. Int Immunopharmacol 2013; 16(1): 85–92 https://doi.org/10.1016/j.intimp.2013.03.020 pmid: 23557965
71	Bai A, Yong M, Ma AG, Ma Y, Weiss CR, Guan Q, Bernstein CN, Peng Z. Novel anti-inflammatory action of 5-aminoimidazole-4-carboxamide ribonucleoside with protective effect in dextran sulfate sodium-induced acute and chronic colitis. J Pharmacol Exp Ther 2010; 333(3): 717–725 https://doi.org/10.1124/jpet.109.164954 pmid: 20237071
72	Son HJ, Lee J, Lee SY, Kim EK, Park MJ, Kim KW, Park SH, Cho ML. Metformin attenuates experimental autoimmune arthritis through reciprocal regulation of Th17/Treg balance and osteoclastogenesis. Mediators Inflamm 2014; 2014: 973986 https://doi.org/10.1155/2014/973986 pmid: 25214721
73	Lee SY, Lee SH, Yang EJ, Kim EK, Kim JK, Shin DY, Cho ML. Metformin ameliorates inflammatory bowel disease by suppression of the STAT3 signaling pathway and regulation of the between Th17/Treg balance. PLoS One 2015; 10(9): e0135858 https://doi.org/10.1371/journal.pone.0135858 pmid: 26360050
74	Bai A, Ma AG, Yong M, Weiss CR, Ma Y, Guan Q, Bernstein CN, Peng Z. AMPK agonist downregulates innate and adaptive immune responses in TNBS-induced murine acute and relapsing colitis. Biochem Pharmacol 2010; 80(11): 1708–1717 https://doi.org/10.1016/j.bcp.2010.08.009 pmid: 20797389
75	Nath N, Giri S, Prasad R, Salem ML, Singh AK, Singh I. 5-aminoimidazole-4-carboxamide ribonucleoside: a novel immunomodulator with therapeutic efficacy in experimental autoimmune encephalomyelitis. J Immunol 2005; 175(1): 566–574 https://doi.org/10.4049/jimmunol.175.1.566 pmid: 15972693
76	Boxer LM, Dang CV. Translocations involving c-myc and c-myc function. Oncogene 2001; 20(40): 5595–5610 https://doi.org/10.1038/sj.onc.1204595 pmid: 11607812
77	Erikson J, ar-Rushdi A, Drwinga HL, Nowell PC, Croce CM. Transcriptional activation of the translocated c-myc oncogene in burkitt lymphoma. Proc Natl Acad Sci USA 1983; 80(3): 820–824 https://doi.org/10.1073/pnas.80.3.820 pmid: 6402776
78	Wang R, Dillon CP, Shi LZ, Milasta S, Carter R, Finkelstein D, McCormick LL, Fitzgerald P, Chi H, Munger J, Green DR. The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity 2011; 35(6): 871–882 https://doi.org/10.1016/j.immuni.2011.09.021 pmid: 22195744
79	Sinclair LV, Rolf J, Emslie E, Shi YB, Taylor PM, Cantrell DA. Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation. Nat Immunol 2013; 14(5): 500–508 https://doi.org/10.1038/ni.2556 pmid: 23525088
80	Molon B, Calì B, Viola A. T cells and cancer: how metabolism shapes immunity. Front Immunol 2016; 7: 20 https://doi.org/10.3389/fimmu.2016.00020 pmid: 26870036
81	Frey AB. Suppression of T cell responses in the tumor microenvironment. Vaccine 2015; 33(51): 7393–7400 https://doi.org/10.1016/j.vaccine.2015.08.096 pmid: 26403368
82	Vinay DS, Ryan EP, Pawelec G, Talib WH, Stagg J, Elkord E, Lichtor T, Decker WK, Whelan RL, Kumara HMCS, Signori E, Honoki K, Georgakilas AG, Amin A, Helferich WG, Boosani CS, Guha G, Ciriolo MR, Chen S, Mohammed SI, Azmi AS, Keith WN, Bilsland A, Bhakta D, Halicka D, Fujii H, Aquilano K, Ashraf SS, Nowsheen S, Yang X, Choi BK, Kwon BS. Immune evasion in cancer: mechanistic basis and therapeutic strategies. Semin Cancer Biol 2015; 35(Suppl): S185–S198 https://doi.org/10.1016/j.semcancer.2015.03.004 pmid: 25818339
83	Kim R, Emi M, Tanabe K. Cancer immunoediting from immune surveillance to immune escape. Immunology 2007; 121(1): 1–14 https://doi.org/10.1111/j.1365-2567.2007.02587.x pmid: 17386080
84	Gajewski TF, Fuertes M, Spaapen R, Zheng Y, Kline J. Molecular profiling to identify relevant immune resistance mechanisms in the tumor microenvironment. Curr Opin Immunol 2011; 23(2): 286–292 https://doi.org/10.1016/j.coi.2010.11.013 pmid: 21185705
85	Bianchi G, Borgonovo G, Pistoia V, Raffaghello L. Immunosuppressive cells and tumour microenvironment: focus on mesenchymal stem cells and myeloid derived suppressor cells. Histol Histopathol 2011; 26(7): 941–951 pmid: 21630223
86	Taylor ES, McCall JL, Girardin A, Munro FM, Black MA, Kemp RA. Functional impairment of infiltrating T cells in human colorectal cancer. OncoImmunology 2016; 5(11): e1234573 https://doi.org/10.1080/2162402X.2016.1234573 pmid: 27999752
87	Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med 2013; 19(11): 1423–1437 https://doi.org/10.1038/nm.3394 pmid: 24202395
88	Herbel C, Patsoukis N, Bardhan K, Seth P, Weaver JD, Boussiotis VA. Clinical significance of T cell metabolic reprogramming in cancer. Clin Transl Med 2016; 5(1): 29 https://doi.org/10.1186/s40169-016-0110-9 pmid: 27510264
89	Chang CH, Qiu J, O’Sullivan D, Buck MD, Noguchi T, Curtis JD, Chen Q, Gindin M, Gubin MM, van der Windt GJ, Tonc E, Schreiber RD, Pearce EJ, Pearce EL. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell 2015; 162(6): 1229–1241 https://doi.org/10.1016/j.cell.2015.08.016 pmid: 26321679
90	Zhang Y, Ertl HC. Starved and asphyxiated: how can CD8+ T cells within a tumor microenvironment prevent tumor progression. Front Immunol 2016; 7: 32 https://doi.org/10.3389/fimmu.2016.00032 pmid: 26904023
91	Nakaigawa N, Kondo K, Ueno D, Namura K, Makiyama K, Kobayashi K, Shioi K, Ikeda I, Kishida T, Kaneta T, Minamimoto R, Tateishi U, Inoue T, Yao M. The acceleration of glucose accumulation in renal cell carcinoma assessed by FDG PET/CT demonstrated acquisition of resistance to tyrosine kinase inhibitor therapy. BMC Cancer 2017; 17(1): 39 https://doi.org/10.1186/s12885-016-3044-0 pmid: 28068944
92	Crespo J, Sun H, Welling TH, Tian Z, Zou W. T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment. Curr Opin Immunol 2013; 25(2): 214–221 https://doi.org/10.1016/j.coi.2012.12.003 pmid: 23298609
93	Chaudhary B, Elkord E. Regulatory T cells in the tumor microenvironment and cancer progression: role and therapeutic targeting. Vaccines (Basel) 2016; 4(3): E28 https://doi.org/10.3390/vaccines4030028 pmid: 27509527
94	Yaqub S, Henjum K, Mahic M, Jahnsen FL, Aandahl EM, Bjørnbeth BA, Taskén K. Regulatory T cells in colorectal cancer patients suppress anti-tumor immune activity in a COX-2 dependent manner. Cancer Immunol Immunother 2008; 57(6): 813–821 https://doi.org/10.1007/s00262-007-0417-x pmid: 17962941
95	Chaudhary B, Abd Al Samid M, al-Ramadi BK, Elkord E. Phenotypic alterations, clinical impact and therapeutic potential of regulatory T cells in cancer. Expert Opin Biol Ther 2014; 14(7): 931–945 https://doi.org/10.1517/14712598.2014.900539 pmid: 24661020
96	Chi H. Regulation and function of mTOR signalling in T cell fate decisions. Nat Rev Immunol 2012; 12(5): 325–338 https://doi.org/10.1038/nri3198 pmid: 22517423
97	Chaube B, Bhat MK. AMPK, a key regulator of metabolic/energy homeostasis and mitochondrial biogenesis in cancer cells. Cell Death Dis 2016; 7(1): e2044 https://doi.org/10.1038/cddis.2015.404 pmid: 26775698

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