The intercellular metabolic interplay between tumor and immune cells

Frontiers in Immunology

Volumn 5, Issue JUL, 2014, Pages

  Wang, Tingting ^a   Liu, Guangwei ^b,c   Wang, Ruoning ^a,d  

^a THE RESEARCH INSTITUTE AT NATIONWIDE CHILDREN S HOSPITAL   (United States)

^b BEIJING UNIVERSITY OF POSTS AND TELECOMMUNICATIONS   (China)

^c FUDAN UNIVERSITY   (China)

^d THE OHIO STATE UNIVERSITY COLLEGE OF MEDICINE   (United States)

Author keywords

Antagonism; Metabolism; Symbiosis; Tumor; Tumor immunity

Indexed keywords

EID: 84905673351     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2014.00358     Document Type: Review

References (119)

1. Belanger M, Allaman I, Magistretti PJ. Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab (2011) 14(6):724-38. doi: 10.1016/j.cmet.2011.08.016
2. Merezhinskaya N, Fishbein WN. Monocarboxylate transporters: past, present, and future. Histol Histopathol (2009) 24(2):243-64.
3. Brooks GA. Cell-cell and intracellular lactate shuttles. J Physiol (2009) 587(Pt 23):5591-600. doi:10.1113/jphysiol.2009.178350
4. Lee KA, Kim SH, Kim EK, Ha EM, You H, Kim B, et al. Bacterial-derived uracil as a modulator of mucosal immunity and gut-microbe homeostasis in Drosophila. Cell (2013) 153(4):797-811. doi:10.1016/j.cell.2013.04.009
5. Baruch M, Belotserkovsky I, Hertzog BB, Ravins M, Dov E, McIver KS, et al. An extracellular bacterial pathogen modulates host metabolism to regulate its own sensing and proliferation. Cell (2014) 156(1-2):97-108. doi:10.1016/j.cell.2013.12.007
6. Donohoe DR, Garge N, Zhang X, Sun W, O'Connell TM, Bunger MK, et al. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab (2011) 13(5):517-26. doi:10.1016/j.cmet.2011.02.018
7. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature (2011) 472(7341):57-63. doi:10.1038/nature09922
8. Zhang W, Trachootham D, Liu J, Chen G, Pelicano H, Garcia-Prieto C, et al. Stromal control of cystine metabolism promotes cancer cell survival in chronic lymphocytic leukaemia. Nat Cell Biol (2012) 14(3):276-86. doi:10.1038/ncb2432
9. Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, et al. The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle (2009) 8(23):3984-4001. doi:10.4161/cc.8.23.10238
10. Das SK, Eder S, Schauer S, Diwoky C, Temmel H, Guertl B, et al. Adipose triglyceride lipase contributes to cancer-associated cachexia. Science (2011) 333(6039):233-8. doi:10.1126/science.1198973
11. Kung HN, Marks JR, Chi JT. Glutamine synthetase is a genetic determinant of cell type-specific glutamine independence in breast epithelia. PLoS Genet (2011) 7(8):e1002229. doi:10.1371/journal.pgen.1002229
12. Roodhart JM, Daenen LG, Stigter EC, Prins HJ, Gerrits J, Houthuijzen JM, et al. Mesenchymal stem cells induce resistance to chemotherapy through the release of platinum-induced fatty acids. Cancer Cell (2011) 20(3):370-83. doi:10.1016/j.ccr.2011.08.010
13. Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med (2011) 17(11):1498-503. doi:10.1038/nm.2492
14. Fiaschi T, Marini A, Giannoni E, Taddei ML, Gandellini P, De Donatis A, et al. Reciprocal metabolic reprogramming through lactate shuttle coordinately influences tumor-stroma interplay. Cancer Res (2012) 72(19):5130-40. doi:10.1158/0008-5472.can-12-1949
15. Sonveaux P, Vegran F, Schroeder T, Wergin MC, Verrax J, Rabbani ZN, et al. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Invest (2008) 118(12):3930-42. doi:10.1172/jci36843
16. June CH. Adoptive T cell therapy for cancer in the clinic. J Clin Invest (2007) 117(6):1466-76. doi:10.1172/jci32446
17. June CH. Principles of adoptive T cell cancer therapy. J Clin Invest (2007) 117(5):1204-12. doi:10.1172/jci31446
18. Leen AM, Rooney CM, Foster AE. Improving T cell therapy for cancer. Annu Rev Immunol (2007) 25:243-65. doi:10.1146/annurev.immunol.25.022106.141527
19. Kershaw MH, Westwood JA, Darcy PK. Gene-engineered T cells for cancer therapy. Nat Rev Cancer (2013) 13(8):525-41. doi:10.1038/nrc3565
20. Cardone RA, Casavola V, Reshkin SJ. The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis. Nat Rev Cancer (2005) 5(10):786-95. doi:10.1038/nrc1713
21. De Milito A, Fais S. Tumor acidity, chemoresistance and proton pump inhibitors. Future Oncol (2005) 1(6):779-86. doi:10.2217/14796694.1.6.779
22. Kato Y, Ozawa S, Miyamoto C, Maehata Y, Suzuki A, Maeda T, et al. Acidic extracellular microenvironment and cancer. Cancer Cell Int (2013) 13(1):89. doi:10.1186/1475-2867-13-89
23. Possemato R, Marks KM, Shaul YD, Pacold ME, Kim D, Birsoy K, et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature (2011) 476(7360):346-50. doi:10.1038/nature10350
24. Locasale JW, Grassian AR, Melman T, Lyssiotis CA, Mattaini KR, Bass AJ, et al. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat Genet (2011) 43(9):869-74. doi:10.1038/ng.890
25. 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
26. Platten MW, Weller M, Wick W. Shaping the glioma immune microenvironment through tryptophan metabolism. CNS Oncol (2012) 1:99-106. doi:10.2217/cns.12.6
27. Tedeschi PM, Markert EK, Gounder M, Lin H, Dvorzhinski D, Dolfi SC, et al. Contribution of serine, folate and glycine metabolism to the ATP, NADPH and purine requirements of cancer cells. Cell Death Dis (2013) 4:e877. doi:10.1038/cddis.2013.393
28. Locasale JW. Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat Rev Cancer (2013) 13(8):572-83. doi:10.1038/nrc3557
29. Wang R, Green DR. The immune diet: meeting the metabolic demands of lymphocyte activation. F1000 Biol Rep (2012) 4:9. doi:10.3410/B4-9
30. Wang R, Green DR. Metabolic reprogramming and metabolic dependency in T cells. Immunol Rev (2012) 249(1):14-26. doi:10.1111/j.1600-065X.2012.01155.x
31. 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
32. Jones RG, Thompson CB. Revving the engine: signal transduction fuels T cell activation. Immunity (2007) 27(2):173-8. doi:10.1016/j.immuni.2007.07.008
33. Pearce EL, Pearce EJ. Metabolic pathways in immune cell activation and quiescence. Immunity (2013) 38(4):633-43. doi:10.1016/j.immuni.2013.04.005
34. Finlay D, Cantrell DA. Metabolism, migration and memory in cytotoxic T cells. Nat Rev Immunol (2011) 11(2):109-17. doi:10.1038/nri2888
35. 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
36. Jacobs SR, Herman CE, Maciver NJ, Wofford JA, Wieman HL, Hammen JJ, et al. Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways. J Immunol (2008) 180(7):4476-86. doi:10.4049/jimmunol.180.7.4476
37. 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
38. Fox CJ, Hammerman PS, Thompson CB. Fuel feeds function: energy metabolism and the T-cell response. Nat Rev Immunol (2005) 5(11):844-52. doi:10.1038/nri1710
39. Caro-Maldonado A, Wang R, Nichols AG, Kuraoka M, Milasta S, Sun LD, et al. Metabolic reprogramming is required for antibody production that is suppressed in anergic but exaggerated in chronically BAFF-exposed B cells. J Immunol (2014) 192(8):3626-36. doi:10.4049/jimmunol.1302062
40. Doughty CA, Bleiman BF, Wagner DJ, Dufort FJ, Mataraza JM, Roberts MF, et al. Antigen receptor-mediated changes in glucose metabolism in B lymphocytes: role of phosphatidylinositol 3-kinase signaling in the glycolytic control of growth. Blood (2006) 107(11):4458-65. doi:10.1182/blood-2005-12-4788
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. 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
43. Dang EV, Barbi J, Yang HY, Jinasena D, Yu H, Zheng Y, et al. Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell (2011) 146(5):772-84. doi:10.1016/j.cell.2011.07.033
44. Sukumar M, Liu J, Ji Y, Subramanian M, Crompton JG, Yu Z, et al. Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function. J Clin Invest (2013) 123(10):4479-88. doi:10.1172/jci69589
45. van der Windt GJ, Pearce EL. Metabolic switching and fuel choice during T-cell differentiation and memory development. Immunol Rev (2012) 249(1):27-42. doi:10.1111/j.1600-065X.2012.01150.x
46. Pantel A, Teixeira A, Haddad E, Wood EG, Steinman RM, Longhi MP. Direct type I IFN but not MDA5/TLR3 activation of dendritic cells is required for maturation and metabolic shift to glycolysis after poly IC stimulation. PLoS Biol (2014) 12(1):e1001759. doi:10.1371/journal.pbio.1001759
47. Krawczyk CM, Holowka T, Sun J, Blagih J, Amiel E, DeBerardinis RJ, et al. Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood (2010) 115(23):4742-9. doi:10.1182/blood-2009-10-249540
48. Herber DL, Cao W, Nefedova Y, Novitskiy SV, Nagaraj S, Tyurin VA, et al. Lipid accumulation and dendritic cell dysfunction in cancer. Nat Med (2010) 16(8):880-6. doi:10.1038/nm.2172
49. Rehman A, Hemmert KC, Ochi A, Jamal M, Henning JR, Barilla R, et al. Role of fatty-acid synthesis in dendritic cell generation and function. J Immunol (2013) 190(9):4640-9. doi:10.4049/jimmunol.1202312
50. Mantovani A. Cancer: inflammation by remote control. Nature (2005) 435(7043):752-3. doi:10.1038/435752a
51. Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer (2004) 4(1):71-8. doi:10.1038/nrc1256
52. Sica A, Schioppa T, Mantovani A, Allavena P. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer (2006) 42(6):717-27. doi:10.1016/j.ejca.2006.01.003
53. Sessa C, De Braud F, Perotti A, Bauer J, Curigliano G, Noberasco C, et al. Trabectedin for women with ovarian carcinoma after treatment with platinum and taxanes fails. J Clin Oncol (2005) 23(9):1867-74. doi:10.1200/jco.2005.09.032
54. Wahl LM, Kleinman HK. Tumor-associated macrophages as targets for cancer therapy. J Natl Cancer Inst (1998) 90(21):1583-4. doi:10.1093/jnci/90.21.1583
55. Giraudo E, Inoue M, Hanahan D. An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis. J Clin Invest (2004) 114(5):623-33. doi:10.1172/jci22087
56. Guiducci C, Vicari AP, Sangaletti S, Trinchieri G, Colombo MP. Redirecting in vivo elicited tumor infiltrating macrophages and dendritic cells towards tumor rejection. Cancer Res (2005) 65(8):3437-46. doi:10.1158/0008-5472.can-04-4262
57. Franklin RA, Liao W, Sarkar A, Kim MV, Bivona MR, Liu K, et al. The cellular and molecular origin of tumor-associated macrophages. Science (2014) 344(6186):921-5. doi:10.1126/science.1252510
58. Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF, Goel G, et al. Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha. Nature (2013) 496(7444):238-42. doi:10.1038/nature11986
59. Stubbs M, Kuhner AV, Glass EA, David JR, Karnovsky ML. Metabolic and functional studies on activated mouse macrophages. J Exp Med (1973) 137(2):537-42. doi:10.1084/jem.137.2.537
60. Newsholme P, Costa Rosa LF, Newsholme EA, Curi R. The importance of fuel metabolism to macrophage function. Cell Biochem Funct (1996) 14(1):1-10. doi:10.1002/cbf.644
61. Vats D, Mukundan L, Odegaard JI, Zhang L, Smith KL, Morel CR, et al. Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation. Cell Metab (2006) 4(1):13-24. doi:10.1016/j.cmet.2006.05.011
62. Lacy-Hulbert A, Moore KJ. Designer macrophages: oxidative metabolism fuels inflammation repair. Cell Metab (2006) 4(1):7-8. doi:10.1016/j.cmet.2006.06.001
63. Johnson AR, Milner JJ, Makowski L. The inflammation highway: metabolism accelerates inflammatory traffic in obesity. Immunol Rev (2012) 249(1):218-38. doi:10.1111/j.1600-065X.2012.01151.x
64. Thompson RW, Pesce JT, Ramalingam T, Wilson MS, White S, Cheever AW, et al. Cationic amino acid transporter-2 regulates immunity by modulating arginase activity. PLoS Pathog (2008) 4(3):e1000023. doi:10.1371/journal.ppat.1000023
65. Qualls JE, Subramanian C, Rafi W, Smith AM, Balouzian L, DeFreitas AA, et al. Sustained generation of nitric oxide and control of mycobacterial infection requires argininosuccinate synthase 1. Cell Host Microbe (2012) 12(3):313-23. doi:10.1016/j.chom.2012.07.012
66. Das P, Lahiri A, Lahiri A, Chakravortty D. Modulation of the arginase pathway in the context of microbial pathogenesis: a metabolic enzyme moonlighting as an immune modulator. PLoS Pathog (2010) 6(6):e1000899. doi:10.1371/journal.ppat.1000899
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. Gordon S. Alternative activation of macrophages. Nat Rev Immunol (2003) 3(1):23-35. doi:10.1038/nri978
69. Liu G, Bi Y, Shen B, Yang H, Zhang Y, Wang X, et al. SIRT1 limits the function and fate of myeloid-derived suppressor cells in tumors by orchestrating HIF-1alpha-dependent glycolysis. Cancer Res (2014) 74(3):727-37. doi:10.1158/0008-5472.can-13-2584
70. Hsu PP, Sabatini DM. Cancer cell metabolism: warburg and beyond. Cell (2008) 134(5):703-7. doi:10.1016/j.cell.2008.08.021
71. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer (2011) 11(2):85-95. doi:10.1038/nrc2981
72. Amelio I, Cutruzzola F, Antonov A, Agostini M, Melino G. Serine and glycine metabolism in cancer. Trends Biochem Sci (2014) 39(4):191-8. doi:10.1016/j.tibs.2014.02.004
73. Estrela JM, Ortega A, Obrador E. Glutathione in cancer biology and therapy. Crit Rev Clin Lab Sci (2006) 43(2):143-81. doi:10.1080/10408360500523878
74. Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov (2009) 8(7):579-91. doi:10.1038/nrd2803
75. Estrella V, Chen T, Lloyd M, Wojtkowiak J, Cornnell HH, Ibrahim-Hashim A, et al. Acidity generated by the tumor microenvironment drives local invasion. Cancer Res (2013) 73(5):1524-35. doi:10.1158/0008-5472.can-12-2796
76. Annibaldi A, Widmann C. Glucose metabolism in cancer cells. Curr Opin Clin Nutr Metab Care (2010) 13(4):466-70. doi:10.1097/MCO.0b013e32833a5577
77. Liang J, Mills GB. AMPK: a contextual oncogene or tumor suppressor? Cancer Res (2013) 73(10):2929-35. doi:10.1158/0008-5472.can-12-3876
78. Sabatini DM. mTOR and cancer: insights into a complex relationship. Nat Rev Cancer (2006) 6(9):729-34. doi:10.1038/nrc1974
79. Reiling JH, Sabatini DM. Stress and mTORture signaling. Oncogene (2006) 25(48):6373-83. doi:10.1038/sj.onc.1209889
80. Vousden KH, Ryan KM. p53 and metabolism. Nat Rev Cancer (2009) 9(10):691-700. doi:10.1038/nrc2715
81. Altman BJ, Rathmell JC. Metabolic stress in autophagy and cell death pathways. Cold Spring Harb Perspect Biol (2012) 4(9):a008763. doi:10.1101/cshperspect.a008763
82. Lob S, Konigsrainer 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
83. Munn DH, Mellor AL. Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J Clin Invest (2007) 117(5):1147-54. doi:10.1172/jci31178
84. Pilotte L, Larrieu P, Stroobant V, Colau D, Dolusic E, Frederick R, et al. Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase. Proc Natl Acad Sci U S A (2012) 109(7):2497-502. doi:10.1073/pnas.1113873109
85. Adams S, Braidy N, Bessede A, Brew BJ, Grant R, Teo C, et al. The kynurenine pathway in brain tumor pathogenesis. Cancer Res (2012) 72(22):5649-57. doi:10.1158/0008-5472.can-12-0549
86. Veldhoen M, Hirota K, Christensen J, O'Garra A, Stockinger B. Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells. J Exp Med (2009) 206(1):43-9. doi:10.1084/jem.20081438
87. Nguyen NT, Hanieh H, Nakahama T, Kishimoto T. The roles of aryl hydrocarbon receptor in immune responses. Int Immunol (2013) 25(6):335-43. doi:10.1093/intimm/dxt011
88. Nguyen NT, Kimura A, Nakahama T, Chinen I, Masuda K, Nohara K, et al. Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism. Proc Natl Acad Sci U S A (2010) 107(46):19961-6. doi:10.1073/pnas.1014465107
89. Mezrich JD, Fechner JH, Zhang X, Johnson BP, Burlingham WJ, Bradfield CA. An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J Immunol (2010) 185(6):3190-8. doi:10.4049/jimmunol.0903670
90. Opitz CA, Litzenburger UM, Sahm F, Ott M, Tritschler I, Trump S, et al. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature (2011) 478(7368):197-203. doi:10.1038/nature10491
91. D'Autreaux B, Toledano MB. ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol (2007) 8(10):813-24. doi:10.1038/nrm2256
92. Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal (2012) 24(5):981-90. doi:10.1016/j.cellsig.2012.01.008
93. Srivastava MK, Sinha P, Clements VK, Rodriguez P, Ostrand-Rosenberg S. Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine. Cancer Res (2010) 70(1):68-77. doi:10.1158/0008-5472.can-09-2587
94. Wink DA, Vodovotz Y, Laval J, Laval F, Dewhirst MW, Mitchell JB. The multifaceted roles of nitric oxide in cancer. Carcinogenesis (1998) 19(5):711-21. doi:10.1093/carcin/19.5.711
95. Fukumura D, Kashiwagi S, Jain RK. The role of nitric oxide in tumour progression. Nat Rev Cancer (2006) 6(7):521-34. doi:10.1038/nrc1910
96. Choudhari SK, Chaudhary M, Bagde S, Gadbail AR, Joshi V. Nitric oxide and cancer: a review. World J Surg Oncol (2013) 11:118. doi:10.1186/1477-7819-11-118
97. Feun L, You M, Wu CJ, Kuo MT, Wangpaichitr M, Spector S, et al. Arginine deprivation as a targeted therapy for cancer. Curr Pharm Des (2008) 14(11):1049-57. doi:10.2174/138161208784246199
98. Lind DS. Arginine and cancer. J Nutr (2004) 134(10 Suppl):2837S-41S.
99. Rodriguez PC, Quiceno DG, Ochoa AC. L-arginine availability regulates T-lymphocyte cell-cycle progression. Blood (2007) 109(4):1568-73. doi:10.1182/blood-2006-06-031856
100. Lamas B, Vergnaud-Gauduchon J, Goncalves-Mendes N, Perche O, Rossary A, Vasson MP, et al. Altered functions of natural killer cells in response to L-Arginine availability. Cell Immunol (2012) 280(2):182-90. doi:10.1016/j.cellimm.2012.11.018
101. Ambs S, Merriam WG, Ogunfusika MO, Bennett WP, Ishibe N, Hussain SP, et al. p53 and vascular endothelial growth factor regulate tumor growth of NOS2-expressing human carcinoma cells. Nat Med (1998) 4(12):1371-6. doi:10.1038/3957
102. Rajnakova A, Moochhala S, Goh PM, Ngoi S. Expression of nitric oxide synthase, cyclooxygenase, and p53 in different stages of human gastric cancer. Cancer Lett (2001) 172(2):177-85. doi:10.1016/S0304-3835(01)00645-0
103. Bonavida B, Baritaki S. Dual role of NO donors in the reversal of tumor cell resistance and EMT: downregulation of the NF-kappaB/Snail/YY1/RKIP circuitry. Nitric Oxide (2011) 24(1):1-7. doi:10.1016/j.niox.2010.10.001
104. Wongvaranon P, Pongrakhananon V, Chunhacha P, Chanvorachote P. Acquired resistance to chemotherapy in lung cancer cells mediated by prolonged nitric oxide exposure. Anticancer Res (2013) 33(12):5433-44.
105. Wachsberger P, Burd R, Dicker AP. Tumor response to ionizing radiation combined with antiangiogenesis or vascular targeting agents: exploring mechanisms of interaction. Clin Cancer Res (2003) 9(6):1957-71.
106. 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
107. Dietl K, Renner K, Dettmer K, Timischl B, Eberhart K, Dorn C, et al. Lactic acid and acidification inhibit TNF secretion and glycolysis of human monocytes. J Immunol (2010) 184(3):1200-9. doi:10.4049/jimmunol.0902584
108. Samuvel DJ, Sundararaj KP, Nareika A, Lopes-Virella MF, Huang Y. Lactate boosts TLR4 signaling and NF-kappaB pathway-mediated gene transcription in macrophages via monocarboxylate transporters and MD-2 up-regulation. J Immunol (2009) 182(4):2476-84. doi:10.4049/jimmunol.0802059
109. Reshkin SJ, Cardone RA, Harguindey S. Na+-H+ exchanger, pH regulation and cancer. Recent Pat Anticancer Drug Discov (2013) 8(1):85-99. doi:10.2174/1574892811308010085
110. Kleinewietfeld M, Manzel A, Titze J, Kvakan H, Yosef N, Linker RA, et al. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature (2013) 496(7446):518-22. doi:10.1038/nature11868
111. Wu C, Yosef N, Thalhamer T, Zhu C, Xiao S, Kishi Y, et al. Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature (2013) 496(7446):513-7. doi:10.1038/nature11984
112. Gladden LB. Lactate metabolism: a new paradigm for the third millennium. J Physiol (2004) 558(Pt 1):5-30. doi:10.1113/jphysiol.2003.058701
113. Philp A, Macdonald AL, Watt PW. Lactate - a signal coordinating cell and systemic function. J Exp Biol (2005) 208(Pt 24):4561-75. doi:10.1242/jeb.01961
114. Dhup S, Dadhich RK, Porporato PE, Sonveaux P. Multiple biological activities of lactic acid in cancer: influences on tumor growth, angiogenesis and metastasis. Curr Pharm Des (2012) 18(10):1319-30. doi:10.2174/138161212799504902
115. Roth S, Droge W. Regulation of interleukin 2 production, interleukin 2 mRNA expression and intracellular glutathione levels in ex vivo derived T lymphocytes by lactate. Eur J Immunol (1991) 21(8):1933-7. doi:10.1002/eji.1830210823
116. Roth S, Gmunder H, Droge W. Regulation of intracellular glutathione levels and lymphocyte functions by lactate. Cell Immunol (1991) 136(1):95-104. doi:10.1016/0008-8749(91)90384-N
117. Husain Z, Huang Y, Seth P, Sukhatme VP. Tumor-derived lactate modifies antitumor immune response: effect on myeloid-derived suppressor cells and NK cells. J Immunol (2013) 191(3):1486-95. doi:10.4049/jimmunol.1202702
118. 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
119. Crowther M, Brown NJ, Bishop ET, Lewis CE. Microenvironmental influence on macrophage regulation of angiogenesis in wounds and malignant tumors. J Leukoc Biol (2001) 70(4):478-90.