T cells and cancer: How metabolism shapes immunity

Frontiers in Immunology

Volumn 7, Issue FEB, 2016, Pages

  Molon, Barbara ^a,b   Calì, Bianca ^a,b   Viola, Antonella ^a,b  

^a UNIVERSITY OF PADOVA   (Italy)

^b VENETIAN INSTITUTE OF MOLECULAR MEDICINE   (Italy)

Author keywords

Immune escape; Immunotherapy; Reactive nitrogen species; T lymphocyte activation; Tumor microenvironment

Indexed keywords

GLUCOSE TRANSPORTER 1;

CANCER IMMUNOTHERAPY; CYTOLOGY; HUMAN; IMMUNITY; LACTATE DEHYDROGENASE BLOOD LEVEL; LYMPHOCYTE ACTIVATION; NEOPLASM; OXIDATIVE PHOSPHORYLATION; OXYGEN CONSUMPTION; OXYGEN TENSION; PROTEIN PROCESSING; SHORT SURVEY; SIGNAL TRANSDUCTION; T LYMPHOCYTE; TUMOR MICROENVIRONMENT;

EID: 84961677958     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2016.00020     Document Type: Short Survey

References (78)

1. Biswas SK. Metabolic reprogramming of immune cells in cancer progression. Immunity (2015) 43(3):435-49. doi: 10.1016/j.immuni.2015.09.001.
2. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell (2011) 144(5):646-74. doi:10.1016/j.cell.2011.02.013.
3. Hirschhaeuser F, Sattler UG, Mueller-Klieser W. Lactate: a metabolic key player in cancer. Cancer Res (2011) 71(22):6921-5. doi:10.1158/0008-5472.CAN-11-1457.
4. Kelloff GJ, Hoffman JM, Johnson B, Scher HI, Siegel BA, Cheng EY, et al. Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clin Cancer Res (2005) 11(8):2785-808. doi:10.1158/1078-0432.CCR-04-2626.
5. Villalba M, Rathore MG, 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):106-13. doi:10.1016/j.biocel.2012.04.024.
6. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science (2006) 313(5795):1960-4. doi:10.1126/science.1129139.
7. Yee C, Thompson JA, Byrd D, Riddell SR, Roche P, Celis E, et al. Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells. Proc Natl Acad Sci U S A (2002) 99(25):16168-73. doi:10.1073/pnas.242600099.
8. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med (2012) 366(26):2443-54. doi:10.1056/NEJMoa1200690.
9. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med (2010) 363(8):711-23. doi:10.1056/NEJMoa1003466.
10. Frauwirth KA, Riley JL, Harris MH, Parry RV, Rathmell JC, Plas DR, et al. The CD28 signaling pathway regulates glucose metabolism. Immunity (2002) 16(6):769-77. doi:10.1016/S1074-7613(02)00323-0.
11. Maciver NJ, Jacobs SR, Wieman HL, Wofford JA, Coloff JL, Rathmell JC. Glucose metabolism in lymphocytes is a regulated process with significant effects on immune cell function and survival. J Leukoc Biol (2008) 84(4):949-57. doi:10.1189/jlb.0108024.
12. MacIver NJ, Michalek RD, Rathmell JC. Metabolic regulation of T lymphocytes. Annu Rev Immunol (2013) 31:259-83. doi:10.1146/annurev-immunol-032712-095956.
13. Chang CH, Curtis JD, Maggi LB Jr, Faubert B, Villarino AV, O'Sullivan D, et al. Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell (2013) 153(6):1239-51. doi:10.1016/j.cell.2013.05.016.
14. Patsoukis N, Bardhan K, Chatterjee P, Sari D, Liu B, Bell LN, et al. PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nat Commun (2015) 6:6692. doi:10.1038/ncomms7692.
15. Zheng Y, Delgoffe GM, Meyer CF, Chan W, Powell JD. Anergic T cells are metabolically anergic. J Immunol (2009) 183(10):6095-101. doi:10.4049/jimmunol.0803510.
16. Rabinowitz JD, White E. Autophagy and metabolism. Science (2010) 330(6009):1344-8. doi:10.1126/science.1193497.
17. Kolev M, Dimeloe S, Le Friec G, Navarini A, Arbore G, Povoleri GA, et al. Complement regulates nutrient influx and metabolic reprogramming during Th1 cell responses. Immunity (2015) 42(6):1033-47. doi:10.1016/j.immuni.2015.05.024.
18. Wieman HL, Wofford JA, Rathmell JC. Cytokine stimulation promotes glucose uptake via phosphatidylinositol-3 kinase/Akt regulation of Glut1 activity and trafficking. Mol Biol Cell (2007) 18(4):1437-46. doi:10.1091/mbc.E06-07-0593.
19. Ghesquière B, Wong BW, Kuchnio A, Carmeliet P. Metabolism of stromal and immune cells in health and disease. Nature (2014) 511(7508):167-76. doi:10.1038/nature13312.
20. Bertout JA, Patel SA, Simon MC. The impact of O2 availability on human cancer. Nat Rev Cancer (2008) 8(12):967-75. doi:10.1038/nrc2540.
21. Imtiyaz HZ, Simon MC. Hypoxia-inducible factors as essential regulators of inflammation. Curr Top Microbiol Immunol (2010) 345:105-20. doi:10.1007/82_2010_74.
22. Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer (2003) 3(10):721-32. doi:10.1038/nrc1187.
23. Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR, et al. HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med (2011) 208(7):1367-76. doi:10.1084/jem.20110278.
24. Dang CV. Glutaminolysis: supplying carbon or nitrogen or both for cancer cells? Cell Cycle (2010) 9(19):3884-6. doi:10.4161/cc.9.19.13302.
25. Wang R, Dillon CP, Shi LZ, Milasta S, Carter R, Finkelstein D, et al. The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity (2011) 35(6):871-82. doi:10.1016/j.immuni.2011.09.021.
26. Cheng SC, Quintin J, Cramer RA, Shepardson KM, Saeed S, Kumar V, et al. mTOR-and HIF-1alpha-mediated aerobic glycolysis as metabolic basis for trained immunity. Science (2014) 345(6204):1250684. doi:10.1126/science.1250684.
27. Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell (2012) 149(2):274-93. doi:10.1016/j.cell.2012.03.017.
28. Siska PJ, Rathmell JC. T cell metabolic fitness in antitumor immunity. Trends Immunol (2015) 36(4):257-64. doi:10.1016/j.it.2015.02.007.
29. 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. doi:10.1016/j.immuni.2009.10.010.
30. Jones RG, Plas DR, Kubek S, Buzzai M, Mu J, Xu Y, et al. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell (2005) 18(3):283-93. doi:10.1016/j.molcel.2005.03.027.
31. Blagih J, Coulombe F, Vincent EE, Dupuy F, Galicia-Vázquez G, Yurchenko E, et al. The energy sensor AMPK regulates T cell metabolic adaptation and effector responses in vivo. Immunity (2015) 42(1):41-54. doi:10.1016/j.immuni.2014.12.030.
32. Rao E, Zhang Y, Zhu G, Hao J, Persson XM, Egilmez NK, et al. Deficiency of AMPK in CD8+ T cells suppresses their anti-tumor function by inducing protein phosphatase-mediated cell death. Oncotarget (2015) 6(10):7944-58. doi:10.18632/oncotarget.3501.
33. Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, et al. Conversion of peripheral CD4+CD25-naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med (2003) 198(12):1875-86. doi:10.1084/jem.20030152.
34. Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med (2004) 10(9):942-9. doi:10.1038/nm1093.
35. Wilke CM, Wu K, Zhao E, Wang G, Zou W. Prognostic significance of regulatory T cells in tumor. Int J Cancer (2010) 127(4):748-58. doi:10.1002/ijc.25464.
36. Salama P, Phillips M, Grieu F, Morris M, Zeps N, Joseph D, et al. Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J Clin Oncol (2009) 27(2):186-92. doi:10.1200/JCO.2008.18.7229.
37. Zhuo C, Li Z, Xu Y, Wang Y, Li Q, Peng J, et al. Higher FOXP3-TSDR demethylation rates in adjacent normal tissues in patients with colon cancer were associated with worse survival. Mol Cancer (2014) 13:153. doi:10.1186/1476-4598-13-153.
38. Correale P, Rotundo MS, Del Vecchio MT, Remondo C, Migali C, Ginanneschi C, et al. Regulatory (FoxP3+) T-cell tumor infiltration is a favorable prognostic factor in advanced colon cancer patients undergoing chemo or chemoimmunotherapy. J Immunother (2010) 33(4):435-41. doi:10.1097/CJI.0b013e3181d32f01.
39. Frey DM, Droeser RA, Viehl CT, Zlobec I, Lugli A, Zingg U, et al. High frequency of tumor-infiltrating FOXP3(+) regulatory T cells predicts improved survival in mismatch repair-proficient colorectal cancer patients. Int J Cancer (2010) 126(11):2635-43. doi:10.1002/ijc.24989.
40. Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC, Deoliveira D, et al. The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab (2014) 20(1):61-72. doi:10.1016/j.cmet.2014.05.004.
41. Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF, et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol (2011) 186(6):3299-303. doi:10.4049/jimmunol.1003613.
42. Shackelford DB, Shaw RJ. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer (2009) 9(8):563-75. doi:10.1038/nrc2676.
43. Murray IA, Patterson AD, Perdew GH. Aryl hydrocarbon receptor ligands in cancer: friend and foe. Nat Rev Cancer (2014) 14(12):801-14. doi:10.1038/nrc3846.
44. Shime H, Yabu M, Akazawa T, Kodama K, Matsumoto M, Seya T, et al. Tumor-secreted lactic acid promotes IL-23/IL-17 proinflammatory pathway. J Immunol (2008) 180(11):7175-83. doi:10.4049/jimmunol.180.11.7175.
45. Gullino PM, Grantham FH. The vascular space of growing tumors. Cancer Res (1964) 24:1727-32.
46. Ho PC, Bihuniak JD, Macintyre AN, Staron M, Liu X, Amezquita R, et al. Phosphoenolpyruvate is a metabolic checkpoint of anti-tumor T cell responses. Cell (2015) 162(6):1217-28. doi:10.1016/j.cell.2015.08.012.
47. Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, et al. Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood (2007) 109(9):3812-9. doi:10.1182/blood-2006-07-035972.
48. Fukumura D, Xu L, Chen Y, Gohongi T, Seed B, Jain RK. Hypoxia and acidosis independently up-regulate vascular endothelial growth factor transcription in brain tumors in vivo. Cancer Res (2001) 61(16):6020-4.
49. Sattler UG, Meyer SS, Quennet V, Hoerner C, Knoerzer H, Fabian C, et al. Glycolytic metabolism and tumour response to fractionated irradiation. Radiother Oncol (2010) 94(1):102-9. doi:10.1016/j.radonc.2009.11.007.
50. Walenta S, Wetterling M, Lehrke M, Schwickert G, Sundfør K, Rofstad EK, et al. High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer Res (2000) 60(4):916-21.
51. Barsoum IB, Smallwood CA, Siemens DR, Graham CH. A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells. Cancer Res (2014) 74(3):665-74. doi:10.1158/0008-5472.CAN-13-0992.
52. Hensley CT, Wasti AT, DeBerardinis RJ. Glutamine and cancer: cell biology, physiology, and clinical opportunities. J Clin Invest (2013) 123(9):3678-84. doi:10.1172/JCI69600.
53. 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):317-52. doi:10.1002/med.20092.
54. Cederbaum SD, Yu H, Grody WW, Kern RM, Yoo P, Iyer RK. Arginases I and II: do their functions overlap? Mol Genet Metab (2004) 81(Suppl 1):S38-44. doi:10.1016/j.ymgme.2003.10.012.
55. Tham M, Tan KW, Keeble J, Wang X, Hubert S, Barron L, et al. Melanoma-initiating cells exploit M2 macrophage TGFbeta and arginase pathway for survival and proliferation. Oncotarget (2014) 5(23):12027-42. doi:10.18632/oncotarget.2482.
56. Brito C, Naviliat M, Tiscornia AC, Vuillier F, Gualco G, Dighiero G, et al. Peroxynitrite inhibits T lymphocyte activation and proliferation by promoting impairment of tyrosine phosphorylation and peroxynitrite-driven apoptotic death. J Immunol (1999) 162(6):3356-66.
57. Aulak KS, Miyagi M, Yan L, West KA, Massillon D, Crabb JW, et al. Proteomic method identifies proteins nitrated in vivo during inflammatory challenge. Proc Natl Acad Sci U S A (2001) 98(21):12056-61. doi:10.1073/pnas.221269198.
58. Radoja S, Frey AB. Cancer-induced defective cytotoxic T lymphocyte effector function: another mechanism how antigenic tumors escape immune-mediated killing. Mol Med (2000) 6(6):465-79.
59. Zippelius A, Batard P, Rubio-Godoy V, Bioley G, Liénard D, Lejeune F, et al. Effector function of human tumor-specific CD8 T cells in melanoma lesions: a state of local functional tolerance. Cancer Res (2004) 64(8):2865-73. doi:10.1158/0008-5472.CAN-03-3066.
60. Bronte V, Kasic T, Gri G, Gallana K, Borsellino G, Marigo I, et al. Boosting antitumor responses of T lymphocytes infiltrating human prostate cancers. J Exp Med (2005) 201(8):1257-68. doi:10.1084/jem.20042028.
61. Nagaraj S, Gupta K, Pisarev V, Kinarsky L, Sherman S, Kang L, et al. Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat Med (2007) 13(7):828-35. doi:10.1038/nm1609.
62. Whiteside TL. Signaling defects in T lymphocytes of patients with malignancy. Cancer Immunol Immunother (1999) 48(7):346-52. doi:10.1007/s002620050585.
63. Kasic T, Colombo P, Soldani C, Wang CM, Miranda E, Roncalli M, et al. Modulation of human T-cell functions by reactive nitrogen species. Eur J Immunol (2011) 41(7):1843-9. doi:10.1002/eji.201040868.
64. Molon B, Ugel S, Del Pozzo F, Soldani C, Zilio S, Avella D, et al. Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells. J Exp Med (2011) 208(10):1949-62. doi:10.1084/jem.20101956.
65. Predonzani A, Calì B, Agnellini AH, Molon B. Spotlights on immunological effects of reactive nitrogen species: when inflammation says nitric oxide. World J Exp Med (2015) 5(2):64-76. doi:10.5493/wjem.v5.i2.64.
66. Rodriguez PC, Quiceno DG, Zabaleta J, Ortiz B, Zea AH, Piazuelo MB, et al. Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res (2004) 64(16):5839-49. doi:10.1158/0008-5472.CAN-04-0465.
67. Bronte V, Zanovello P. Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol (2005) 5(8):641-54. doi:10.1038/nri1668.
68. Munn DH, Mellor AL. Indoleamine 2,3 dioxygenase and metabolic control of immune responses. Trends Immunol (2013) 34(3):137-43. doi:10.1016/j.it.2012.10.001.
69. Löb S, Königsrainer A, Rammensee HG, Opelz G, Terness P. Inhibitors of indoleamine-2,3-dioxygenase for cancer therapy: can we see the wood for the trees? Nat Rev Cancer (2009) 9(6):445-52. doi:10.1038/nrc2639.
70. Vacchelli E, Aranda F, Eggermont A, Sautès-Fridman C, Tartour E, Kennedy EP, et al. Trial watch: IDO inhibitors in cancer therapy. Oncoimmunology (2014) 3(10):e957994. doi:10.4161/21624011.2014.957994.
71. Weinlich G, Murr C, Richardsen L, Winkler C, Fuchs D. Decreased serum tryptophan concentration predicts poor prognosis in malignant melanoma patients. Dermatology (2007) 214(1):8-14. doi:10.1159/000096906.
72. Godin-Ethier J, Hanafi LA, Piccirillo CA, Lapointe R. Indoleamine 2,3-dioxygenase expression in human cancers: clinical and immunologic perspectives. Clin Cancer Res (2011) 17(22):6985-91. doi:10.1158/1078-0432.CCR-11-1331.
73. van Baren N, Van den Eynde BJ. Tryptophan-degrading enzymes in tumoral immune resistance. Front Immunol (2015) 6:34. doi:10.3389/fimmu.2015.00034.
74. Riesenberg R, Weiler C, Spring O, Eder M, Buchner A, Popp T, et al. Expression of indoleamine 2,3-dioxygenase in tumor endothelial cells correlates with long-term survival of patients with renal cell carcinoma. Clin Cancer Res (2007) 13(23):6993-7002. doi:10.1158/1078-0432.CCR-07-0942.
75. Gottfried E, Kreutz M, Mackensen A. Tumor metabolism as modulator of immune response and tumor progression. Semin Cancer Biol (2012) 22(4):335-41. doi:10.1016/j.semcancer.2012.02.009.
76. Platten M, Wick W, Van den Eynde BJ. Tryptophan catabolism in cancer: beyond IDO and tryptophan depletion. Cancer Res (2012) 72(21):5435-40. doi:10.1158/0008-5472.CAN-12-0569.
77. Uyttenhove C, Pilotte L, Théate I, Stroobant V, Colau D, Parmentier N, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med (2003) 9(10):1269-74. doi:10.1038/nm934.
78. Liu X, Shin N, Koblish HK, Yang G, Wang Q, Wang K, et al. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood (2010) 115(17):3520-30. doi:10.1182/blood-2009-09-246124.