Adenosine as an endogenous immunoregulator in cancer pathogenesis: Where to go?

Purinergic Signalling

Volumn 9, Issue 2, 2013, Pages 145-165

  Kumar, V ^a,b  

^a QUEEN S UNIVERSITY   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

Adenosine; Cancer; DCs; Inflammation; Macrophages; MDSCs; NK cells; T cells; Tregs; Tumor

Indexed keywords

ADENOSINE; CD4 ANTIGEN; CYCLOOXYGENASE 2; GAMMA INTERFERON; HYPOXIA INDUCIBLE FACTOR 1ALPHA; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 4; TRANSCRIPTION FACTOR FOXP3; TUMOR NECROSIS FACTOR ALPHA; VASCULOTROPIN;

CELL INTERACTION; DENDRITIC CELL; HUMAN; INFLAMMATION; LYMPHOCYTIC INFILTRATION; MACROPHAGE; NATURAL KILLER CELL; NEOPLASM; NONHUMAN; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; REVIEW; SUPPRESSOR CELL; T LYMPHOCYTE; TUMOR MICROENVIRONMENT;

ADENOSINE; ANIMALS; HUMANS; IMMUNOLOGIC FACTORS; NEOPLASMS;

EID: 84877615153     PISSN: 15739538     EISSN: 15739546     Source Type: Journal    
DOI: 10.1007/s11302-012-9349-9     Document Type: Review

References (243)

1. Cao Ya, DePinho RA, Ernst M, Vousden K (2011) Cancer research: past, present and future. Nat Rev Cancer 11: 749-754.
2. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144: 646-674.
3. Bissel MJ, Hines WC (2011) Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat Med 17: 20-29.
4. Moore PS, Chang Y (2010) Why do viruses cause cancer? Highlights of the first century of human tumor virology. Nat Rev Cancer 10: 878-889.
5. Parkin DM (2006) The global health burden of infection-associated cancer sin the year 2002. Int J Cancer 118: 3030-3044.
6. Trinchieri G (2012) Cancer and inflammation: an old intuition with rapidly evolving new concepts. Annu Rev Immunol 30: 677-706.
7. Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357: 539-545.
8. Balkwill F, Charles KA, Mantovani A (2005) Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7: 211-217.
9. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420: 860-867.
10. Karin M (2006) Nuclear factor-κB in cancer development and progression. Nature 441: 431-436.
11. Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454: 436-444.
12. Reedy J (1975) Galen on cancer and related diseases. Clio Med 10: 227-238.
13. Pierce BL, Ballard-Barbash R, Bernstein L, Baumgartner RN, Neuhouser ML, Wener MH, Baumgartner KB, Gilliland FD, Sorensen BE, McTiernan A, Ulrich CM (2009) Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients. J Clin Oncol 27: 3437-3444.
14. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A (2009) Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30(7): 1073-1081.
15. Zitvogel L, Apetoh L, Ghiringhelli F, André F, Tesniere A, Kroemer G (2008) The anticancer immune response: indispensable for therapeutic success? J Clin Invest 118(6): 1991-2001.
16. Schreiber RD, Old LJ, Smyth MJ (2011) Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 331(6024): 1565-1570.
17. Bindea G, Mlecnik B, Fridman WH, Galon J (2011) The prognostic impact of anti-cancer immune response: a novel classification of cancer patients. Semin Immunopathol 33(4): 335-340.
18. Dunwiddie TV, Masino SA (2001) The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci 24: 1-55.
19. Schuh SM, Hille B, Babcock DF (2007) Adenosine and catecholamine agonists speed the flagellar beat of mammalian sperm by a non-receptor-mediated mechanism. Biol Reprod 77: 960-969.
20. Hove-Madsen L, Prat-Vidal C, Llach A, Ciruela F, Casado V, Lluis C, Bayes-Genis A, Cinca J, Franco R (2006) Adenosine A2A receptors are expressed in human atrial myocytes and modulate spontaneous sarcoplasmic reticulum calcium release. Cardiovasc Res 72: 292-302.
21. Okusa MD (2002) A(2A) adenosine receptor: a novel therapeutic target in renal disease. Am J Physiol Ren Physiol 282: F10-F18.
22. Spicuzza L, Di Maria G, Polosa R (2006) Adenosine in the airways: implications and applications. Eur J Pharmacol 533: 77-88.
23. Fredholm BB, Ijezerman AP, Jacobson KA, Klotz KN, Linden J (2001) International union of pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53: 527-552.
24. Martin C, Leone M, Viviand X, Ayem ML, Guieu R (2000) High adenosine plasma concentration as a prognostic index for outcome in patients with septic shock. Crit Care Med 28: 3198-3202.
25. Sperlagh B, Doda M, Baranyi M, Hasko G (2000) Ischemia-like condition releases norepinephrine and purines from different sources in superfused rat spleen strips. J Neuroimmunol 111: 45-54.
26. Drury AN, Szent-Gyorgyi A (1929) The physiological activity of adenine compounds with especial reference to their action upon the mammalian heart. J Physiol 68: 213-237.
27. Newby AC (1984) Adenosine and the concept of retaliatory metabolites. Trends Biochem Sci 9: 42-44.
28. Hasko G, Cronstein BN (2004) Adenosine: an endogenous regulator of innate immunity. Trends Immunol 25: 33-39.
29. Antonioli L, Fornai M, Colucci R, Ghisu N, Tuccori M, Tacca MD, Blandizzi C (2008) Pharmacological modulation of adenosine system: novel options for treatment of inflammatory bowel diseases. Inflamm Bowel Dis 14(4): 566-574.
30. Cabrita MA, Baldwin SA, Young JD, Cass CE (2002) Molecular biology and regulation of nucleoside and nucleobase transporter proteins in eukaryotes and prokaryotes. Biochem Cell Biol 80: 623-638.
31. Pastor-Anglada M, Casado FJ, Valdes R, Mata J, Garcia-Manteiga J, Molina M (2001) Complex regulation of nucleoside transporter expression in epithelial and immune system cells. Mol Membr Biol 18: 81-85.
32. Noji T, Karasawa A, Kusaka H (2004) Adenosine uptake inhibitors. Eur J Pharmacol 495: 1-16.
33. Linden J (2001) Molecular approach to adenosine receptors: receptor-mediated mechanisms of tissue protection. Annu Rev Pharmacol Toxicol 41: 775-787.
34. Hasko G, Kuhel DG, Nemeth ZH, Mabley JG, Stachlewitz RF, Virag L, Lohinai Z, Southan GJ, Salzman AL, Szabo C (2000) Inosine inhibits inflammatory cytokine production by a posttranscriptional mechanism and protects against endotoxin-induced shock. J Immunol 164: 1013-1019.
35. Mabley JG, Pacher P, Liaudet L, Soriano FG, Hasko G, Marton A, Szabo C, Salzman AL (2003) Inosine reduces inflammation and improves survival in a murine model of colitis. Am J Physiol Gastrointest Liver Physiol 284: G138-G144.
36. Scott GS, Spitsin SV, Kean RB, Mikheeva T, Koprowski H, Hooper DC (2002) Therapeutic intervention in experimental allergic encephalomyelitis by administration of uric acid precursors. Proc Natl Acad Sci USA 99: 16303-16308.
37. Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8: 958-969.
38. Stefater JA III, Ren S, Lang RA, Duffield JS (2011) Metchnikoff's policemen: macrophages in development, homeostasis and regeneration. Trends Immunol 17(12): 743-752.
39. Condeelis J, Pollard JW (2006) Macrophages: obligate partners for tumor cell migration, invasion and metastasis. Cell 124: 263-266.
40. Qian B-Z, Pollard JW (2010) Macrophage diversity enhances tumor progression and metastasis. Cell 141: 39-51.
41. Gordon S, Taylor PR (2005) Monocyte and macrophage heterogeneity. Nat Rev Immunol 5: 953-964.
42. Gordon S (2007) Macrophages: past, present and future. Eur J Immunol 37: S9-S17.
43. Mackaness GB (1977) Cellular immunity and parasite. Adv Exp Med Biol 93: 65-73.
44. O'Shea JJ, Murray PJ (2008) Cytokine signaling modules in inflammatory responses. Immunity 28: 477-487.
45. Tahir SMA, Cheng O, Shaulov A, Koezuka Y, Bubley GJ, Wilson SB, Balk SP, Exley MA (2001) Loss of IFN-γ production by invariant NK T cells in advanced cancer. J Immunol 167: 4046-4050.
46. Menard C, Blay J-Y, Borg C, Michiels S, Ghiringhelli F, Robert C, Nonn C, Chaput N, Taïeb J, Delahaye NF, Flament C, Emile JF, Le Cesne A, Zitvogel L (2009) Natural killer cell IFN-γ levels predict long-term survival with Imatinib Mesylate therapy in gastrointestinal stromal tumor-bearing patients. Cancer Res 69: 3563-3569.
47. Swan JB, Vesely MD, Silva A, Sharkey J, Akira A, Schreiber RD, Smyth MJ (2008) Demonstration of inflammation-induced cancer and cancer immunoediting during primary tumorigenesis. Proc Natl Acad Sci USA 105: 652-656.
48. Nathan CF (1987) Secretory products of macrophages. J Clin Invest 79: 319-326.
49. MacMicking J, Xie QW, Nathan C (1997) Nitric oxide and macrophage function. Annu Rev Immunol 15: 323-350.
50. Romieu-Mourez R, Solis M, Nardin A, Goubau D, Baron-Bodo V, Lin R, Massie B, Salcedo M, Hiscott J (2006) Distinct role of IFN regulatory factor (IRF)-3 and IRF-7 in the activation of anti-tumor properties of human macrophages. Cancer Res 66: 10576-10585.
51. Lamagna C, Aurrand-Lions M, Imhof BA (2006) Dual role of macrophages on tumor growth and angiogenesis. J Leukoc Biol 80: 705-713.
52. Heusinkveld M, van der Burg SH (2011) Identification and manipulation of tumor associated macrophages in human cancers. J Transl Med 9: 216-228.
53. Heusinkveld M, de Vos van Steenwijk PJ, Goedemans R, Ramwadhdoebe TH, Gorter A, Welters MJ, van Hall T, van der Burg SH (2011) M2 macrophages induced by prostaglandin E2 and IL-6 from cervical carcinoma are switched to activated M1 macrophages by CD4+ Th1 cells. J Immunol 187(3): 1157-1165.
54. Andreu P, Johansson M, Affara NI, Pucci F, Tan T, Junankar S, Korets L, Lam J, Tawfik D, DeNardo DG, Naldini L, de Visser KE, De Palma M, Coussens LM (2010) FcRγ activation regulates inflammation associated squamous cell carcinogenesis. Cancer Cell 17(2): 121-134.
55. De Visser KE, Korets LV, Coussens LM (2005) De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell 7: 411-423.
56. Kryczek I, Zou L, Rodriguez P, Zhu G, Wei S, Mottram P, Brumlik M, Cheng P, Curiel T, Myers L, Lackner A, Alvarez X, Ochoa A, Chen L, Zou W (2006) B7-H4 expression identifies a novel suppressive macrophage population human ovarian carcinoma. J Exp Med 203: 871-881.
57. Nardin A, Anastado JP (2008) Macrophages and cancer. Front Biosci 13: 3494-3505.
58. Sierra JR, Corso S, Caione L, Cepero V, Conrotto P, Cignetti A, Piacibello W, Kumanogoh A, Kikutani H, Comoglio PM, Tamagnone L, Giordano S (2008) Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor associated macrophages. J Exp Med 205: 1673-1685.
59. + immature myeloid cells. Nat Med 7: 87-95.
60. Raleigh JA, Calkins-Adams DP, Rinker LH, Ballenger CA, Weissler MC, Fowler WC Jr, Novotny DB, Varia MA (1998) Hypoxia and vascular endothelial growth factor expression in human squamous cell carcinomas using pimonidazole as a hypoxia marker. Cancer Res 58: 3765-3768.
61. Raskovalova T, Huang X, Sitkovsky M, Zacharia LC, Jackson EK, Gorelik E (2005) Gs protein-coupled adenosine receptor signaling and lytic function of activated NK cells. J Immunol 175: 4383-4391.
62. Blay J, White TD, Hoskin DW (1997) The extracellular fluid of solid carcinomas contains immunosuppressive concentrations of adenosine. Cancer Res 57: 2602-2605.
63. 2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci USA 103: 13132-13137.
64. Morimoto C, Schlossman SF (1998) The structure and function of CD26 in the T-cell immune response. Immunol Rev 161: 55-70.
65. Richard E, Alam SM, Arredondo-Vega FX, Patel DD, Hershfield MS (2002) Clustered charged amino acids of human adenosine deaminase comprise a functional epitope for binding the adenosine deaminase complexing protein CD26/dipeptidyl peptidase IV. J Biol Chem 277: 19720-19726.
66. Tan EY, Mujoomdar M, Blay J (2004) Adenosine down-regulates the surface expression of dipeptidyl peptidase IV on HT-29 human colorectal carcinoma cells: implications for cancer cell behaviour. Am J Pathol 165: 319-330.
67. Tan EY, Richard CL, Zhang H, Hoskin DW, Blay J (2006) Adenosine down-regulates DPPIV on HT-29 colon cancer cells by stimulating protein tyrosine phosphatase(s) and reducing ERK1/2 activity via a novel pathway. Am J Physiol Cell Physiol 291: C433-C444.
68. Hasko G, Pacher P, Deitch EA, Vizi ES (2007) Shaping of monocyte and macrophage function by adenosine receptors. Pharmacol Ther 113: 264-275.
69. Fischer D, van der Weyden MB, Snyderman R, Kelley WN (1976) A role for adenosine deaminase in human monocyte maturation. J Clin Invest 58: 399-407.
70. Najar HM, Ruhl S, Bru-Capdeville AC, Peters JH (1990) Adenosine and its derivatives control human monocyte differentiation into highly accessory cells versus macrophages. J Leukoc Biol 47: 429-439.
71. 1 receptor promotion of multinucleated giant cell formation by human monocytes: a mechanism for methotrexate-induced nodulosis in rheumatoid arthritis. Arthritis Rheum 40: 1308-1315.
72. kip-1 expression. J Immunol 163: 4140-4149.
73. 2A receptors in inflammation and injury: lessons learned from transgenic animals. J Leukoc Biol 83(3): 447-455.
74. Lin EY, Li JF, Gnatovskiy L, Deng Y, Zhu L, Grzesik DA, Qian H, Xue XN, Pollard JW (2006) Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res 66: 11238-11246.
75. Pollard JW (2009) Trophic macrophages in development and disease. Nat Rev Immunol 9: 259-270.
76. Wyckoff JB, Wang Y, Lin EY, Li JF, Goswami S, Stanley ER, Segall JE, Pollard JW, Condeelis J (2007) Direct visualization of macrophage-associated tumor cell intravasation in mammary tumors. Cancer Res 67: 2649-2656.
77. Smith HO, Anderson PS, Kuo DY, Goldberg GL, DeVictoria CL, Boocock CA, Jones JG, Runowicz CD, Stanley ER, Pollard JW (1995) The role of colony stimulating factor 1 and its receptor in the etiopathogensis of endometrial adenocarcinoma. Clin Cancer Res 1: 313-325.
78. Lewis CE, Pollard JW (2006) Distinct role of macrophages in different tumor microenvironments. Cancer Res Cancer Res 66: 605-612.
79. Lin EY, Ngyuen AV, Russell RG, Pollard JW (2001) Colony stimulating factor-1 promotes progression of mammary tumors to malignancy. J Exp Med 193: 727-740.
80. Hamilton JA (2008) Colony stimulating factors in inflammation and autoimmunity. Nat Rev Imunol 8: 533-544.
81. +T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell 16: 91-102.
82. Imhof BA, Aurrand-Lions M (2004) Adhesion mechanisms regulating the migration of monocytes. Nat Rev Immunol 4: 432-444.
83. Ribatti D, Nico B, Crivellato E, Vacca A (2007) Macrophages and tumor angiogenesis. Leukemia 21: 2085-2089.
84. Knowles HJ, Haris AL (2007) Macrophages and the hypoxic tumor environment. Front Biosci 4298-4314.
85. Sica A, Bronte V (2007) Altered macrophage differentiation and immune dysfunction in tumor development. J Ciln Invest 117: 1155-1166.
86. Lewis CE, De Palma M, Naldini L (2007) Tie-2 expressing monocytes and tumor angiogenesis: regulation of hypoxia and angiopoietin-2. Cancer Res 67: 8429-8432.
87. Gocheva V, Wang HW, Gadea BB, Shree T, Hunter KE, Garfall AL, Berman T, Joyce JA (2010) IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev 24: 241-255.
88. Schnurr M, Toy T, Shin A, Wagner M, Cebon J, Maraskovsky E (2005) Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and enhances IL-23 expression in human dendritic cells: a novel role for the cAMP pathway. Blood 105(4): 1582-1589.
89. Brunda MJ, Gately MK (1995) Interleukin-12: potential role in cancer therapy. In: DeVita VT, Hellman S, Rosenberg SA (eds) Important advances in oncology 1995. J. B. Lippincott, Philadelphia, pp 3-18.
90. Nastala CL, Edington HD, McKinney TG et al (1994) Recombinant IL-12 administration induces tumor regression in association with IFN-γ production. J Immunol 153: 1697-1706.
91. Brunda MJ, Luistro L, Warrier RR, Wright RB, Hubbard BR, Murphy M, Wolf SF, Gately MK (1993) Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J Exp Med 178(4): 1223-1230.
92. Mu J, Zou J-P, Yamamoto N, Tsutsui T, Tai XG, Kobayashi M, Herrmann S, Fujiwara H, Hamaoka T (1995) Administration of recombinant interleukin 12 prevents outgrowth of tumor cells metastasizing spontaneously to lung and lymph nodes. Cancer Res 55: 4404-4408.
93. Zou J-P, Yamamoto N, Fujii T, Takenaka H, Kobayashi M, Herrmann SH, Wolf SF, Fujiwara H, Hamaoka T (1995) Systemic administration of rIL-12 induces complete tumor regression and protective immunity: response is correlated with a striking reversal of suppressed IFN-γ production by anti-tumor T cells. Int Immunol 7: 1135-1145.
94. Noguchi Y, Richards EC, Chen Y-T, Old LG (1995) Influence of interleukin 12 on p53 peptide vaccination against established Meth A sarcoma. Proc Natl Acad Sci USA 92: 2219-2223.
95. Roberston MJ, Ritz J (1996) Interleukin 12: basic biology and potential applications and cancer treatment. Oncologist 1: 88-97.
96. Coughlin CM, Wysocka M, Kurzawa HL, Lee WM, Trinchieri G, Eck SL (1995) B7-1 and interleukin 12 synergistically induce effective antitumor immunity. Cancer Res 55: 4980-4987.
97. Stern LL, Tarby CM, Tamborini B (1994) Preclinical development of IL-12 as an anticancer drug: comparison to IL-2. Proc Am Soc Cancer Res 35: 520a.
98. Broussas M, Cornillet-Lefebvre P, Potron G, Nguyen P (2002) Adenosine inhibits tissue factor expression by LPS-stimulated human monocytes: involvement of the A3 adenosine receptor. Thromb Haemost 88: 123-130.
99. Gabazza EC, Hayashi T, Ido M, Adachi Y, Suzuki K (2002) Adenosine inhibits thrombin-induced expression of tissue factor on endothelial cells by a nitric oxide-mediated mechanism. Clin Sci (Lond) 102(2): 167-175.
100. Im JH, Fu W, Wang H, Bhatia SK, Hammer DA, Kowalska MA, Muschel RJ (2004) Coagulation facilitates tumor cell spreading in the pulmonary vasculature during early metastatic colony formation. Cancer Res 64(23): 8613-8619.
101. Palumbo JS (2008) Mechanisms linking tumor cell-associated procoagulant function to tumor dissemination. Semin Thromb Hemost 34(2): 154-160.
102. Kasthuri RS, Taubman MB, Mackman N (2009) Role of tissue factor in cancer. J Clin Oncol 27(29): 4834-4838.
103. Adair TH (2005) Growth regulation of the vascular system: an emerging role for adenosine. Am J Physiol Regul Integr Comp Physiol 289: R283-R296.
104. 2A receptor agonists and endotoxin. Am J Pathol 160: 2231-2244.
105. Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9(3): 162-174.
106. Youn JI, Nagaraj S, Collazo M, Gabrilovich DI (2008) Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J Immunol 181(8): 5791-5802.
107. Je-In Y, Collazo M, Shalova IN, Biswas SK, Gabrilovich DI (2012) Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice. J Leukoc Biol 91(1): 167-181.
108. Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC, Carbone DP, Gabrilovich DI (2001) Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol 166(1): 678-689.
109. Filipazzi P, Valenti R, Huber V, Pilla L, Canese P, Iero M, Castelli C, Mariani L, Parmiani G, Rivoltini L (2007) Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. J Clin Oncol 25(18): 2546-2553.
110. Poschke I, Mougiakakos D, Hansson J, Masucci GV, Kiessling R (2010) Immature immunosuppressive CD14 + HLA-DR-/low cells in melanoma patients are Stat3hi and overexpress CD80, CD83, and DC-sign. Cancer Res 70(11): 4335-4345.
111. Srivastava MK, Bosch JJ, Thompson JA, Ksander BR, Edelman MJ, Ostrand-Rosenberg S (2008) Lung cancer patients' CD4(+) T cells are activated in vitro by MHC II cell-based vaccines despite the presence of myeloid-derived suppressor cells. Cancer Immunol Immunother 57(10): 1493-1504.
112. + T lymphocytes in patients with advanced-stage non-small cell lung cancer. J Cancer Res Clin Oncol 136(1): 35-45.
113. Corzo CA, Condamine T, Lu L, Cotter MJ, Youn JI, Cheng P, Cho HI, Celis E, Quiceno DG, Padhya T, McCaffrey TV, McCaffrey JC, Gabrilovich DI (2010) HIF-1α regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J Exp Med 207(11): 2439-2453.
114. Zimmermann W, Kammerer R (2011) Negativer regulators in cancer immunology and immunotherapy. In: J Medin, D Fowler (eds) Experimental and applied immunotherapy.
115. Kusmartsev S, Gabrilovich DI (2006) Role of immature myeloid cells in mechanisms of immune evasion in cancer. Cancer Immunol Immunother 55: 237-245.
116. Rabinovich GA, Gabrilovich D, Sotomayor EM (2007) Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol 25: 267-296.
117. Sica A, Bronte V (2007) Altered macrophage differentiation and immune dysfunction in tumor development. J Clin Invest 117: 1155-1166.
118. Allavena P, Sica A, Garlanda C, Mantovani A (2008) The yin-yang of tumor-associated macrophages in neoplastic progression and immune surveillance. Immunol Rev 222: 155-161.
119. Serafini P, Borrello I, Bronte V (2006) Myeloid suppressor cells in cancer: recruitment, phenotype, properties, and mechanisms of immune suppression. Semin Cancer Biol 16(1): 53-65.
120. Marigo I, Dolcetti L, Serafini P, Zanovello P, Bronte V (2008) Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells. Immunol Rev 222: 162-179.
121. + cells. J Immunol 187(11): 6120-6129.
122. Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392: 245-252.
123. Reise Sousa C (2006) Dendritic cells in a mature age. Nat Rev Immunol 6: 476-483.
124. Steinman RM (2007) Dendritic cells: versatile controllers of the immune system. Nat Med 13(10): 1155-1159.
125. Panther E, Idzko M, Herouy Y, Rheinen H, Gebicke-Haerter PJ, Mrowietz U, Dichmann S, Norgauer J (2001) Expression and function of adenosine receptors in human dendritic cells. FASEB J 15: 1963-1970.
126. Fossetta J, Jackson J, Deno G, Fan X, Du XK, Bober L, Soudé-Bermejo A, de Bouteiller O, Caux C, Lunn C, Lundell D, Palmer RK (2003) Pharmacological analysis of calcium responses mediated by the human A3 adenosine receptor in monocyte-derived dendritic cells and recombinant cells. Mol Pharmacol 63: 342-350.
127. Panther E, Corniti S, Idzko M, Herouy Y, Napp M, Sala AI, Girolomoni G, Norgauer J (2003) Adenosine affects expression of membrane molecules, cytokine and chemokine release, and the T-cell stimulatory capacity of human dendritic cells. Blood 101: 3985-3990.
128. Liu M, Guo S, Stiles JK (2011) The emerging role of CXCL10 in cancer (Review). Oncol Lett 2: 583-589.
129. Mizukami Y, Kono K, Kawaguchi Y, Akaike H, Kamimura K, Sugai H, Fujii H (2008) CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3+ regulatory T cells in gastric cancer. Int J Cancer 122(10): 2286-2293.
130. Kang S, Xie J, Ma S, Liao W, Zhang J, Luo R (2010) Targeted knock down of CCL22 and CCL17 by siRNA during DC differentiation and maturation affects the recruitment of T subsets. Immunobiology 215(2): 153-162.
131. 2B receptors in regulation of dendritic cell differentiation and function. FASEB J 22: 1065. 34.
132. Novitskiy SV, Ryzhov S, Zaynagetdinov R, Goldstein AE, Huang Y, Tikhomirov OY, Blackburn MR, Biaggioni I, Carbone DP, Feoktistov I, Dikov MM (2008) Adenosine receptors in regulation of dendritic cell differentiation and function. Blood 112(5): 1822-1833.
133. Raulet DH (1999) Development and tolerance of natural killer cells. Curr Opin Immunol 11: 129-134.
134. Scott P, Trinchieri G (1995) The role of natural killer cells in host-parasite interactions. Curr Opin Immunol 7: 34-40.
135. Unanue ER (1997) Inter-relationship among macrophages, natural killer cells and neutrophils in early stages of Listeria resistance. Curr Opin Immunol 9: 35-43.
136. Biron CA, Brossay L (2001) NK cells and NKT cells in innate defense against viral infections. Curr Opin Immunol 13: 458-464.
137. Flodstrom M, Shi F-D, Sarvetnick N, Ljunggren H-G (2002) The natural killer cell-friend or foe in autoimmune disease? Scand J Immunol 55: 432-441.
138. Colucci F, Caliguri MA, Di Santo JP (2003) What does it take to make a natural killer. Nat Rev Immunol 3: 413-425.
139. Kumar V, Medhi B (2008) Emerging role of uterine natural killer cells in establishing pregnancy. Iran J Immunol 5(2): 71-81.
140. Backstrom E, Kristensson K, Ljunggren H-G (2004) Activation of natural killer cells: underlying molecular mechanisms revealed. Scand J Immunol 60: 14-22.
141. Miller JS, Cervenka J, Lund J, Okazaki IJ, Moss J (1999) Purine metabolites suppress proliferation of human NK cells through a lineage-specific purine receptor. J Immunol 162: 7376-7382.
142. Arie H, Gil H, Pnina F, Oshra A, Sara B-Y (2003) A3 adenosine receptor agonist potentiates natural killer cell activity. Int J Oncol 23: 1245-1249.
143. Hoskin DW, Mader JS, Furlong JS, Conrad DM, Blay J (2008) Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (Review). Int J Oncol 32: 527-535.
144. Lokshin A, Raskovalova T, Huang X, Zacharia LC, Jackson EK, Gorelik (2006) Adenosine-mediated inhibition of the cytotoxic activity and cytokine production by activated natural killer cells. Cancer Res 66: 7758-7765.
145. Williams BA, Manzer A, Blay J, Hoskin DW (1997) Adenosine acts through a novel extracellular receptor to inhibit granule exocytosis by natural killer cells. Biochem Biophys Res Commun 231: 264-269.
146. Lee SM, Suen Y, Qian J, Knoppel E, Cairo MS (1998) The regulation and biological activity of interleukin 12. Leuk Lymphoma 29: 427-438.
147. Hershfield MS (2005) New insights into adenosine-receptor mediated immunosuppression and the role of adenosine in causing the immunodeficiency associated with adenosine deaminase deficiency. Eu J Immunol 35: 25-30.
148. Gessi S, Varani K, Merighi S, Fogil E, Sacchetto V, Benini A et al (2007) Adenosine and lymphocyte regulation. Purinergic Signal 3: 109-116.
149. Buckley RH (2004) Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Annu Rev Immunol 22: 625-655.
150. Lukashev DE, Smith PT, Caldwell CC, Ohta A, Apasov SG, Sitkovsky MV (2003) Analysis of A2a receptor deficient mice reveals no significant compensatory increases in the expression of A2b, A1, and A3 adenosine receptors in lymphoid organs. Biochem Pharmacol 65: 2081-2090.
151. Gessi S, Varani K, Merighi S, Cattabriga E, Pancaldi C, Szabadkai Y, Rizzuto R, Klotz KN, Leung E, Mac Lennan S, Baraldi PG, Borea PA (2005) Expression, pharmacological profile, and functional coupling of A2B receptors in a recombinant system and in peripheral blood cells using a novel selective antagonist radio ligand, [3H]MRE 2029-F20. Mol Pharmacol 67: 2137-2147.
152. Mirabet M, Herrera C, Cordero OJ, Mallol J, Lluis C, Franco R (1999) Expression of A2B adenosine receptors in human lymphocytes: their role in T cell activation. J Cell Sci 112: 491-502.
153. Schultz LA, Kammer GM, Rudolph SA (1988) Characterization of the human T lymphocyte adenosine receptor: comparison of normal and systemic lupus erythematosus cells. FASEB J 2: 244-250.
154. Merighi S, Mirandola P, Varani K, Gessi S, Leung E, Baraldi PG, Tabrizi MA, Borea PA (2003) A glance at adenosine receptors: novel target for antitumor therapy. Pharmacol Ther 100: 31-48.
155. Hoskin DW, Reynolds T, Blay J (1994) Adenosine as a possible inhibitor of killer T-cell activation in the microenvironment of solid tumors. Int J Cancer 59(6): 854-855.
156. 3 adenosine receptor as a new target for cancer therapy and chemoprotection. Exp Cell Res 269: 230-236.
157. Gadangi P, Longaker M, Naime D, Levin RI, Recht PA, Montesinos MC, Buckley MT, Carlin G, Cronstein BN (1996) The anti-inflammatory mechanism of sulfasalazine is related to adenosine release at inflamed sites. J Immunol 156: 1937-1941.
158. Cronstein BN (1996) Molecular therapeutics. Methotrexate and its mechanism of action. Arthritis Rheum 39: 1951-1960.
159. Zhang H, Conrad DM, Butler JJ, Zhao C, Blay J, Hoskin DW (2004) Adenosine acts through A2 receptors to inhibit IL-2-induced tyrosine phosphorylation of STAT5 in T lymphocytes: role of cyclic adenosine 3′, 5′-monophosphate and phosphatases. J Immunol 173(2): 932-944.
160. Naganuma M, Wiznerowicz EB, Lappas CM, Linden J, Worthington MT, Ernst PB (2006) Cutting edge: critical role for A2A adenosine receptors in the T cell-mediated regulation of colitis. J Immunol 177: 2765-2769.
161. Odashima M, Bamias G, Rivera-Nieves J, Linden J, Nast CC, Moskaluk CA, Marini M, Sugawara K, Kozaiwa K, Otaka M, Watanabe S, Cominelli F (2005) Activation of A2A adenosine receptor attenuates intestinal inflammation in animal models of inflammatory bowel disease. Gastroenterology 129: 26-33.
162. Linden J, Rieger JM, Cunha FQ, Guerrant RL, Ribeiro RA, Brito GA (2006) Effect of novel A2A adenosine receptor agonist ATL 313 on Clostridium difficile toxin A-induced murine ileal enteritis. Infect Immun 74: 2606-2612.
163. Kobie JJ, Shah PR, Yang L, Rebhahn JA, Fowell DJ, Mosmann TR (2006) T regulatory and primed uncommitted CD4 T cells express CD73, which suppresses effector CD4 T cells by converting 5′-adenosine monophosphate to adenosine. J Immunol 177(10): 6780-6786.
164. 2A receptor antagonists: blockade of adenosinergic effects and T regulatory cells. Br J Pharmacol 153: 5457-5464.
165. Lukashev D, Sitkovsky M, Ohta A (2007) From "Hellstorm Paradox" to anti-adenosinergic cancer immunotherapy. Purinergic Signal 3: 129-134.
166. Clayton A, Al-Taei S, Webber J, Mason MD, Tabi Z (2011) Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production. J Immunol 187: 673-683.
167. Zou W (2006) Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 6(4): 295-307.
168. Byrne WL, Mills KGH, Lederer JA, O'Sullivan GC (2011) Targeting regulatory T cells in tumor. Cancer Res 71: 6915-6920.
169. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M (1995) Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25): breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 155: 1151-1164.
170. Sakaguchi S (2004) Naturally arising CD4 regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 22: 531-562.
171. Sakaguchi S (2005) Naturally arising Foxp3-expressing CD25CD4 regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 6: 345-352.
172. Mills KH, McGuirk P (2004) Antigen-specific regulatory T cells-their induction and role in infection. Semin Immunol 16: 107-117.
173. Vigouroux S, Yvon E, Biagi E, Brenner MK (2004) Antigen-induced regulatory T cells. Blood 104: 26-33.
174. + regulatory T cells in immune tolerance. Annu Rev Immunol 30: 733-758.
175. Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299: 1057-1061.
176. + regulatory T cells. Nat Immunol 4: 330-336.
177. + T regulatory cells. Nat Immunol 4: 337-342.
178. Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, Kelly TE, Saulsbury FT, Chance PF, Ochs HD (2001) The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 27: 20-21.
179. Brunkow ME, Jeffery EW, Hjerrild KA, Paeper B, Clark LB, Yasayko SA, Wilkinson JE, Galas D, Ziegler SF, Ramsdell F (2001) Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet 27: 68-73.
180. + T regulatory cells in humans. Hum Immunol 66: 13-20.
181. + T cells. J Clin Invest 112: 1437-1443.
182. + Tregs. J Clin Invest 115: 3276-3284.
183. + regulatory T cells. J Immunol 175: 4180-4183.
184. + regulatory T cells suppress NKT cell functions. Cancer Res 63: 4516-4520.
185. + T regulatory cells: crosstalk between two professionals in immunity versus tolerance. Front Biosci 11: 1360-1370.
186. hi T regulatory cells. Eur J Immunol 35: 2452-2458.
187. + and NK lymphocytes in the direct cell-to-cell interaction. Clin Immunol 112: 258-267.
188. + T cells. Proc Natl Acad Sci USA 99: 8832-8837.
189. Read S, Malmstrom V, Powrie F (2000) Cytotoxic T lymophocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med 192: 295-302.
190. Takahashi T, Tagami T, Yamazaki S, Uede T, Shimizu J, Sakaguchi N, Mak TW, Sakaguchi S (2000) Immunologic self-tolerance maintained by CD25(+) CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med 192: 303-310.
191. McHugh RS, Whitters MJ, Piccirillo CA, Young DA, Shevach EM, Collins M, Byrne MC (2002) CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 16: 311-323.
192. Shimizu J, Yamazaki S, Takahashi T, Ishida Y, Sakaguchi S (2002) Stimulation of CD25(+)CD4(+)regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol 3: 135-142.
193. Beyer M, Schultze JL (2006) Regulatory T cells in cancer. Blood 108(3): 804-811.
194. high suppressor T cells mediate potent effector T cell blockade and cause failure of otherwise curative adoptive immunotherapy. J Immunol 169: 4811-4821.
195. Wang R-F (2006) Regulatory T cells and innate immune regulation in tumor immunity. Semin Immunol 28: 17-23.
196. Roncarolo MG, Levings MK (2000) The role of different subsets of T regulatory cells in controlling autoimmunity. Curr Opin Immunol 12: 676-683.
197. Francois Bach J (2003) Regulatory T cells under scrutiny. Nat Rev Immunol 3: 189-198.
198. Weiner HL (2001) Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells. Immunol Rev 182: 207-214.
199. Colombo MP, Piconese S (2007) Regulatory T-cell inhibition versus depletion: the right choice in cancer immunotherapy. Nat Rev Cancer 7: 880-887.
200. Elkord E, Alcantar-Orozco EM, Dovedi SJ, Tran DQ, Hawkins RE, Gilham DE (2010) T regulatory cells in cancer: recent advances and therapeutic potential. Expert Opin Biol Ther 10(11): 1573-1586.
201. +regulatory T cell proliferation. J Exp Med 202: 919-929.
202. Gorelik L, Flavell RA (2001) Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells. Nat Med 7: 1118-1122.
203. Thomas DA, Massague J (2005) TGF-β directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell 8: 369-380.
204. + cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. J Exp Med 201: 779-791.
205. + regulatory T-cells in cancer. Immunol Res 32: 155-168.
206. Hiura T, Kagamu H, Miura S, Ishida A, Tanaka H, Tanaka J, Gejyo F, Yoshizawa H (2005) Both regulatory T cells and antitumor effector T cells are primed in the same draining lymph nodes during tumor progression. J Immunol 175: 5058-5066.
207. - lymphocytes is thymus and proliferation independent. Cancer Res 66: 4488-4495.
208. + regulatory T cells suppress anti-tumor immune responses in patients with colorectal cancer. PLoS One 1: e129.
209. Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10: 942-949.
210. + regulatory T cells in patients with gastrointestinal malignancies: possible involvement of regulatory T cells in disease progression. Cancer 98: 1089-1099.
211. + regulatory T cells in the peripheral circulation of patients with head and neck cancer. Br J Cancer 92: 913-920.
212. Hontsu S, Yoneyama H, Ueha S, Terashima Y, Kitabatake M, Nakano A, Ito T, Kimura H, Matsushima K (2004) Visualization of naturally occurring Foxp3 regulatory T cells in normal and tumor-bearing mice. Int Immunopharmacol 4: 1785-1793.
213. +T cells. J Immunol 175: 1483-1490.
214. +T regulatory cell activities in lung cancer. Cancer Res 65: 5211-5220.
215. Sitkovsky MV (2009) T regulatory cells: hypoxia-adenosinergic suppression and re-direction of the immune response. Trends Immunol 30(3): 102-108.
216. Wolf D, Wolf AM, Rumpold H, Fiegl H, Zeimet AG, Muller-Holzner E, Deibl M, Gastl G, Gunsilius E, Marth C (2005) The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res 11(23): 8326-8331.
217. Petersen RP, Campa MJ, Sperlazza J, Conlon D, Joshi MB, Harpole DH Jr, Patz EF Jr (2006) Tumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients. Cancer 107(12): 2866-2872.
218. Ishida T, Ishii T, Inagaki A, Yano H, Komatsu H, Iida S, Inagaki H, Ueda R (2006) Specific recruitment of CC chemokine receptor 4-positive regulatory T cells in Hodgkin lymphoma fosters immune privilege. Cancer Res 66(11): 5716-5722.
219. Haas J, Schopp L, Storch-Hagenlocher B, Fritzsching B, Jacobi C, Milkova L, Fritz B, Schwarz A, Suri-Payer E, Hensel M, Wildemann B (2008) Specific recruitment of regulatory T cells into the CSF in lymphomatous and carcinomatous meningitis. Blood 111(2): 761-766.
220. Nummer D, Suri-Payer E, Schmitz-Winnenthal H, Bonertz A, Galindo L, Antolovich D, Koch M, Büchler M, Weitz J, Schirrmacher V, Beckhove P (2007) Role of tumor endothelium in CD4+ CD25+ regulatory T cell infiltration of human pancreatic carcinoma. J Natl Cancer Inst 99(15): 1188-1199.
221. Tan MC, Goedegebuure PS, Belt BA, Flaherty B, Sankpal N, Gillanders WE, Eberlein TJ, Hsieh CS, Linehan DC (2009) Disruption of CCR5-dependent homing of regulatory T cells inhibits tumor growth in a murine model of pancreatic cancer. J Immunol 182(3): 1746-1755.
222. reg cells: hydrolysis of extracellular ATP and immune suppression. Blood 110(4): 1225-1232.
223. Deaglio S, Dwyer KM, Gao W, Friedman D, Usheva A, Erat A, Chen JF, Enjyoji K, Linden J, Oukka M, Kuchroo VK, Strom TB, Robson SC (2007) Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med 204(6): 1257-1265.
224. Onishi Y, Fehervari Z, Yamaguchi T, Sakaguchi S (2008) Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation. Proc Natl Acad Sci USA 105(29): 10113-10118.
225. Zarek PE, Huang CT, Lutz ER, Kowalski J, Horton MR, Linden J, Drake CG, Powell JD (2008) A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells. Blood 111(1): 251-259.
226. Bopp T, Becker C, Klein M, Klein-Hessling S, Palmetshofer A, Serfling E, Heib V, Becker M, Kubach J, Schmitt S, Stoll S, Schild H, Staege MS, Stassen M, Jonuleit H, Schmitt E (2007) Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression. J Exp Med 204(6): 1303-1310.
227. 3 adenosine receptor gene in mice and its effect on stimulated inflammatory cells. J Biol Chem 275: 4429-4434.
228. Sitkovsky MV, Kjaergaard J, Lukashev D, Ohta A (2008) Hypoxia-adenosinergic immunosuppression: tumor protection by T regulatory cells and cancerous tissue hypoxia. Clin Cancer Res 14(19): 5947-5952.
229. 3 adenosine receptor agonists. Drug Discov Today 17(7/8): 359-366.
230. Varani K, Vincenzi F, Targa M, Paradiso B, Parrilli A, Fini M, Lanza G, Borea PA (2012) The stimulation of A(3) adenosine receptors reduces bone-residing breast cancer in a rat preclinical model. Eur J Cancer Jul 5 [Epub ahead of print].
231. Decking UK, Schlieper G, Kroll K, Schrader J (1997) Hypoxia-induced inhibition of adenosine kinase potentiates cardiac adenosine release. Circ Res 81(2): 154-164.
232. Sitkovsky M, Lukashev D (2005) Regulation of immune cells by local tissue oxygen tension: HIF-1α and adenosine receptors. Nat Rev Immunol 5: 712-721.
233. Lukashev D, Ohta A, Sitkovsky M (2007) Hypoxia-dependent anti-inflammatory pathways in protection of cancerous tissues. Cancer Metastasis Rev 26: 273-279.
234. + T lymphocytes. J Immunol 177: 4962-4965.
235. 2A adenosine receptor as a physiological immunosuppressor and to engineer inflammation in vivo. Biochem Pharmacol 65: 493-501.
236. Burnstock G (1972) Purinergic nerve. Pharmacol Rev 24: 509-581.
237. Ohta A, Sitkovsky M (2001) Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature 414: 916-920.
238. 2A receptors. Annu Rev Immunol 22: 657-682.
239. Koshiba M, Kojima H, Huang S, Apasov S, Sitkovsky MV (1997) Memory of extracellular adenosine/A2a purinergic receptor-mediated signalling in murine T cells. J Biol Chem 272: 25881-25889.
240. Huang S, Apasov S, Koshiba M, Sitkovsky M (1997) Role of A2a adenosine receptor-mediated signaling in inhibition of T cell activation and expansion. Blood 90: 1600-1610.
241. Armstrong JM, Chen JF, Schwarzschild MA, Apasov S, Smith PT, Caldwell C, Chen P, Figler H, Sullivan G, Fink S, Linden J, Sitkovsky M (2001) Gene dose effect reveals no Gs-coupled A2A adenosine receptor reserve in murine T-lymphocytes: studies of cells from A2A-receptor-gene- deficient mice. Biochem J 354: 123-130.
242. Kojima H, Gu H, Nomura S, Caldwell CC, Kobata T, Carmeliet P, Semenza GL, Sitkovsky MV (2002) Abnormal B lymphocyte development and autoimmunity in hypoxia-inducible factor 1alpha-deficient chimeric mice. Proc Natl Acad Sci USA 99(4): 2170-2174.
243. Thiel M, Caldwell CC, Kreth S, Kuboki S, Chen P, Smith P, Ohta A, Lentsch AB, Lukashev D, Sitkovsky MV (2007) Targeted deletion of HIF-1alpha gene in T cells prevents their inhibition in hypoxic inflamed tissues and improves septic mice survival. PLoS One 2(9): e853.