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Journal of Biomedicine and Biotechnology
Volume 2012 (2012), Article ID 473712, 9 pages
http://dx.doi.org/10.1155/2012/473712
Research Article

Production of Adenosine by Ectonucleotidases: A Key Factor in Tumor Immunoescape

1INSERM U866, 21078 Dijon, France
2Faculté de Médecine, Université de Bourgogne, 21079 Dijon, France
3Department of Medical Oncology, Centre Georges François Leclerc, 21000 Dijon, France

Received 18 May 2012; Accepted 3 July 2012

Academic Editor: Karen M. Dwyer

Copyright © 2012 François Ghiringhelli et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. D. Schreiber, L. J. Old, and M. J. Smyth, “Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion,” Science, vol. 331, no. 6024, pp. 1565–1570, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. I. Mellman, G. Coukos, and G. Dranoff, “Cancer immunotherapy comes of age,” Nature, vol. 480, no. 7378, pp. 480–489, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. F. Pagès, A. Berger, M. Camus et al., “Effector memory T cells, early metastasis, and survival in colorectal cancer,” New England Journal of Medicine, vol. 353, no. 25, pp. 2654–2666, 2005. View at Publisher · View at Google Scholar · View at Scopus
  4. W. H. Fridman, F. Pagès, C. Sautès-Fridman, and J. Galon, “The immune contexture in human tumours: impact on clinical outcome,” Nature Reviews Cancer, vol. 12, no. 4, pp. 298–306, 2012. View at Publisher · View at Google Scholar · View at Scopus
  5. W. H. Fridman, J. Galon, F. Pagès, E. Tartour, C. Sautès-Fridman, and G. Kroemer, “Prognostic and predictive impact of intra- and peritumoral immune infiltrates,” Cancer Research, vol. 71, no. 17, pp. 5601–5605, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. F. Ghiringhelli, C. Ménard, M. Terme et al., “CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-β-dependent manner,” Journal of Experimental Medicine, vol. 202, no. 8, pp. 1075–1085, 2005. View at Publisher · View at Google Scholar · View at Scopus
  7. F. Ghiringhelli, P. E. Puig, S. Roux et al., “Tumor cells convert immature myeloid dendritic cells into TGF-β-secreting cells inducing CD4+CD25+ regulatory T cell proliferation,” Journal of Experimental Medicine, vol. 202, no. 7, pp. 919–929, 2005. View at Publisher · View at Google Scholar · View at Scopus
  8. J. Vincent, G. Mignot, F. Chalmin et al., “5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity,” Cancer Research, vol. 70, no. 8, pp. 3052–3061, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. H. Suzuki, S. Takatsuka, H. Akashi et al., “Genome-wide profiling of chromatin signatures reveals epigenetic regulation of microRNA genes in colorectal cancer,” Cancer Research, vol. 71, no. 17, pp. 5646–5658, 2011. View at Publisher · View at Google Scholar · View at Scopus
  10. F. Ghiringhelli, L. Apetoh, A. Tesniere et al., “Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β-dependent adaptive immunity against tumors,” Nature Medicine, vol. 15, no. 10, pp. 1170–1178, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. L. Apetoh, F. Ghiringhelli, A. Tesniere et al., “Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy,” Nature Medicine, vol. 13, no. 9, pp. 1050–1059, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. L. Zitvogel, L. Apetoh, F. Ghiringhelli, and G. Kroemer, “Immunological aspects of cancer chemotherapy,” Nature Reviews Immunology, vol. 8, no. 1, pp. 59–73, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. D. M. Pardoll, “The blockade of immune checkpoints in cancer immunotherapy,” Nature Reviews Cancer, vol. 12, no. 4, pp. 252–264, 2012. View at Publisher · View at Google Scholar · View at Scopus
  14. D. S. Martin, J. R. Bertino, and J. A. Koutcher, “ATP depletion + pyrimidine depletion can markedly enhance cancer therapy: fresh insight for a new approach,” Cancer Research, vol. 60, no. 24, pp. 6776–6783, 2000. View at Google Scholar · View at Scopus
  15. B. Sperlágh, F. Erdélyi, G. Szabó, and E. S. Vizi, “Local regulation of [3H]-noradrenaline release from the isolated guinea-pig right atrium by P2X-receptors located on axon terminals,” British Journal of Pharmacology, vol. 131, no. 8, pp. 1775–1783, 2000. View at Google Scholar · View at Scopus
  16. B. B. Fredholm, E. Irenius, B. Kull, and G. Schulte, “Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in Chinese hamster ovary cells,” Biochemical Pharmacology, vol. 61, no. 4, pp. 443–448, 2001. View at Publisher · View at Google Scholar · View at Scopus
  17. S. Gessi, S. Merighi, V. Sacchetto, C. Simioni, and P. A. Borea, “Adenosine receptors and cancer,” Biochimica et Biophysica Acta, vol. 1808, no. 5, pp. 1400–1412, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. G. Haskó and B. N. Cronstein, “Adenosine: an endogenous regulator of innate immunity,” Trends in Immunology, vol. 25, no. 1, pp. 33–39, 2004. View at Publisher · View at Google Scholar · View at Scopus
  19. Y. Inoue, Y. Chen, R. Pauzenberger, M. I. Hirsh, and W. G. Jnger, “Hypertonic saline up-regulates A3 adenosine receptor expression of activated neutrophils and increases acute lung injury after sepsis,” Critical Care Medicine, vol. 36, no. 9, pp. 2569–2575, 2008. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Grinberg, G. Hasko, D. Wu, and S. J. Leibovich, “Suppression of PLCβ2 by endotoxin plays a role in the adenosine A2A receptor-mediated switch of macrophages from an inflammatory to an angiogenic phenotype,” American Journal of Pathology, vol. 175, no. 6, pp. 2439–2453, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. S. Ryzhov, S. V. Novitskiy, A. E. Goldstein et al., “Adenosinergic regulation of the expansion and immunosuppressive activity of CD11b+Gr1 + cells,” Journal of Immunology, vol. 187, no. 11, pp. 6120–6129, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. J. S. Miller, T. Cervenka, J. Lund, I. J. Okazaki, and J. Moss, “Purine metabolites suppress proliferation of human NK cells through a lineage-specific purine receptor,” Journal of Immunology, vol. 162, no. 12, pp. 7376–7382, 1999. View at Google Scholar · View at Scopus
  23. T. Raskovalova, X. Huang, M. Sitkovsky, L. C. Zacharia, E. K. Jackson, and E. Gorelik, “GS protein-coupled adenosine receptor signaling and lytic function of activated NK cells,” Journal of Immunology, vol. 175, no. 7, pp. 4383–4391, 2005. View at Google Scholar · View at Scopus
  24. M. Nowak, L. Lynch, S. Yue et al., “The A2aR adenosine receptor controls cytokine production in iNKT cells,” European Journal of Immunology, vol. 40, no. 3, pp. 682–687, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. S. V. Novitskiy, S. Ryzhov, R. Zaynagetdinov et al., “Adenosine receptors in regulation of dendritic cell differentiation and function,” Blood, vol. 112, no. 5, pp. 1822–1831, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. J. M. Wilson, C. C. Kurtz, S. G. Black et al., “The A2B adenosine receptor promotes Th17 differentiation via stimulation of dendritic cell IL-6,” Journal of Immunology, vol. 186, no. 12, pp. 6746–6752, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. C. M. Lappas, G. W. Sullivan, and J. Linden, “Adenosine A2A agonists in development for the treatment of inflammation,” Expert Opinion on Investigational Drugs, vol. 14, no. 7, pp. 797–806, 2005. View at Publisher · View at Google Scholar · View at Scopus
  28. P. E. Zarek, C. T. Huang, E. R. Lutz et al., “A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells,” Blood, vol. 111, no. 1, pp. 251–259, 2008. View at Publisher · View at Google Scholar · View at Scopus
  29. A. Mirza, A. Basso, S. Black et al., “RNA interference targeting of A1 receptor-overexpressing breast carcinoma cells leads to diminished rates of cell proliferation and induction of apoptosis,” Cancer Biology and Therapy, vol. 4, no. 12, pp. 1355–1360, 2005. View at Google Scholar · View at Scopus
  30. B. Koscsó, B. Csóka, P. Pacher, and G. Haskó, “Investigational A3 adenosine receptor targeting agents,” Expert Opinion on Investigational Drugs, vol. 20, no. 6, pp. 757–768, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. S. Merighi, A. Benini, P. Mirandola et al., “Hypoxia inhibits paclitaxel-induced apoptosis through adenosine-mediated phosphorylation of bad in glioblastoma cells,” Molecular Pharmacology, vol. 72, no. 1, pp. 162–172, 2007. View at Publisher · View at Google Scholar · View at Scopus
  32. S. Merighi, A. Benini, P. Mirandola et al., “Adenosine modulates vascular endothelial growth factor expression via hypoxia-inducible factor-1 in human glioblastoma cells,” Biochemical Pharmacology, vol. 72, no. 1, pp. 19–31, 2006. View at Publisher · View at Google Scholar · View at Scopus
  33. S. Merighi, A. Benini, P. Mirandola et al., “A3 adenosine receptors modulate hypoxia-inducible factor-1α expression in human A375 melanoma cells,” Neoplasia, vol. 7, no. 10, pp. 894–903, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. I. Feoktistov, S. Ryzhov, A. E. Goldstein, and I. Biaggioni, “Mast cell-mediated stimulation of angiogenesis: cooperative interaction between A2B and A3 adenosine receptors,” Circulation Research, vol. 92, no. 5, pp. 485–492, 2003. View at Publisher · View at Google Scholar · View at Scopus
  35. S. Serra, A. L. Horenstein, T. Vaisitti et al., “CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death,” Blood, vol. 118, no. 23, pp. 6141–6152, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. R. J. Rickles, W. F. Tam, T. P. Giordano et al., “Adenosine A2A and Beta-2 adrenergic receptor agonists: novel selective and synergistic multiple myeloma targets discovered through systematic combination screening,” Molecular Cancer Therapeutics, vol. 11, no. 7, pp. 1432–1442, 2012. View at Google Scholar
  37. S. Merighi, P. Mirandola, D. Milani et al., “Adenosine receptors as mediators of both cell proliferation and cell death of cultured human melanoma cells,” Journal of Investigative Dermatology, vol. 119, no. 4, pp. 923–933, 2002. View at Publisher · View at Google Scholar · View at Scopus
  38. J. W. Fisher and J. Brookins, “Adenosine A2A and A2B receptor activation of erythropoietin production,” American Journal of Physiology, vol. 281, no. 5, pp. F826–F832, 2001. View at Google Scholar · View at Scopus
  39. A. J. Zatta, G. P. Matherne, and J. P. Headrick, “Adenosine receptor-mediated coronary vascular protection in post-ischemic mouse heart,” Life Sciences, vol. 78, no. 21, pp. 2426–2437, 2006. View at Publisher · View at Google Scholar · View at Scopus
  40. H. Takagi, G. L. King, G. S. Robinson, N. Ferrara, and L. P. Aiello, “Adenosine mediates hypoxic induction of vascular endothelial growth factor in retinal pericytes and endothelial cells,” Investigative Ophthalmology and Visual Science, vol. 37, no. 11, pp. 2165–2176, 1996. View at Google Scholar · View at Scopus
  41. M. Iino, R. Ehama, Y. Nakazawa et al., “Adenosine stimulates fibroblast growth factor-7 gene expression via adenosine A2B receptor signaling in dermal papilla cells,” Journal of Investigative Dermatology, vol. 127, no. 6, pp. 1318–1325, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. S. Gessi, E. Fogli, V. Sacchetto et al., “Adenosine modulates HIF-1α, VEGF, IL-8, and foam cell formation in a human model of hypoxic foam cells,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 1, pp. 90–97, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. J. F. Vazquez, H. W. Clement, O. Sommer, E. Schulz, and D. Van Calker, “Local stimulation of the adenosine A2B receptors induces an increased release of IL-6 in mouse striatum: an in vivo microdialysis study,” Journal of Neurochemistry, vol. 105, no. 3, pp. 904–909, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. A. M. Kas-Deelen, W. W. Bakker, P. Olinga et al., “Cytomegalovirus infection increases the expression and activity of ecto-ATPase (CD39) and ecto-5′nucleotidase (CD73) on endothelial cells,” FEBS Letters, vol. 491, no. 1-2, pp. 21–25, 2001. View at Publisher · View at Google Scholar · View at Scopus
  45. G. S. Kansas, G. S. Wood, and T. F. Tedder, “Expression, distribution, and biochemistry of human CD39: role in activation-associated homotypic adhesion of lymphocytes,” Journal of Immunology, vol. 146, no. 7, pp. 2235–2244, 1991. View at Google Scholar · View at Scopus
  46. K. Koziak, J. Sévigny, S. C. Robson, J. B. Siegel, and E. Kaczmarek, “Analysis of CD39/ATP diphosphohydrolase (ATPDase) expression in endothelial cells, platelets and leukocytes,” Thrombosis and Haemostasis, vol. 82, no. 5, pp. 1538–1544, 1999. View at Google Scholar · View at Scopus
  47. S. C. Robson, J. Sévigny, and H. Zimmermann, “The E-NTPDase family of ectonucleotidases: structure function relationships and pathophysiological significance,” Purinergic Signalling, vol. 2, no. 2, pp. 409–430, 2006. View at Publisher · View at Google Scholar · View at Scopus
  48. K. M. Dwyer, S. Deaglio, W. Gao, D. Friedman, T. B. Strom, and S. C. Robson, “CD39 and control of cellular immune responses,” Purinergic Signalling, vol. 3, no. 1-2, pp. 171–180, 2007. View at Publisher · View at Google Scholar · View at Scopus
  49. R. Resta, Y. Yamashita, and L. F. Thompson, “Ecto-enzyme and signaling functions of lymphocyte CD73,” Immunological Reviews, vol. 161, pp. 95–109, 1998. View at Publisher · View at Google Scholar · View at Scopus
  50. L. Yang, J. J. Kobie, and T. R. Mosmann, “CD73 and Ly-6A/E distinguish in vivo primed but uncommitted mouse CD4 T cells from type 1 or type 2 effector cells,” Journal of Immunology, vol. 175, no. 10, pp. 6458–6464, 2005. View at Google Scholar · View at Scopus
  51. Y. Yamashita, S. W. Hooker, H. Jiang et al., “CD73 expression and fyn-dependent signaling on murine lymphocytes,” European Journal of Immunology, vol. 28, no. 10, pp. 2981–2990, 1998. View at Publisher · View at Google Scholar · View at Scopus
  52. L. Airas, “CD73 and adhesion of B-cells to follicular dendritic cells,” Leukemia and Lymphoma, vol. 29, no. 1-2, pp. 37–47, 1998. View at Google Scholar · View at Scopus
  53. G. R. Strohmeier, W. I. Lencer, T. W. Patapoff et al., “Surface expression, polarization, and functional significance of CD73 in human intestinal epithelia,” Journal of Clinical Investigation, vol. 99, no. 11, pp. 2588–2601, 1997. View at Google Scholar · View at Scopus
  54. E. Nemoto, R. Kunii, H. Tada, T. Tsubahara, H. Ishihata, and H. Shimauchi, “Expression of CD73/ecto-5′-nucleotidase on human gingival fibroblasts and contribution to the inhibition of interleukin-1α-induced granulocyte-macrophage colony stimulating factor production,” Journal of Periodontal Research, vol. 39, no. 1, pp. 10–19, 2004. View at Publisher · View at Google Scholar · View at Scopus
  55. K. Synnestvedt, G. T. Furuta, K. M. Comerford et al., “Ecto-5′-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia,” Journal of Clinical Investigation, vol. 110, no. 7, pp. 993–1002, 2002. View at Publisher · View at Google Scholar · View at Scopus
  56. H. K. Eltzschig, J. C. Ibla, G. T. Furuta et al., “Coordinated adenine nucleotide phosphohydrolysis and nucleoside signaling in posthypoxic endothelium: role of ectonucleotidases and adenosine A2B receptors,” Journal of Experimental Medicine, vol. 198, no. 5, pp. 783–796, 2003. View at Publisher · View at Google Scholar · View at Scopus
  57. S. Ledoux, I. Runembert, K. Koumanov, J. B. Michel, G. Trugnan, and G. Friedlander, “Hypoxia enhances Ecto-5′-nucleotidase activity and cell surface expression in endothelial cells: role of membrane lipids,” Circulation Research, vol. 92, no. 8, pp. 848–855, 2003. View at Publisher · View at Google Scholar · View at Scopus
  58. K. Kalsi, C. Lawson, M. Dominguez, P. Taylor, M. H. Yacoub, and R. T. Smolenski, “Regulation of ecto-5′-nucleotidase by TNF-α in human endothelial cells,” Molecular and Cellular Biochemistry, vol. 232, no. 1-2, pp. 113–119, 2002. View at Publisher · View at Google Scholar · View at Scopus
  59. L. Dalh Christensen and V. Andersen, “Natural killer cells lack ecto-5'-nucleotidase,” Natural Immunity, vol. 11, no. 1, pp. 1–6, 1992. View at Google Scholar · View at Scopus
  60. F. S. Regateiro, D. Howie, K. F. Nolan et al., “Generation of anti-inflammatory adenosine byleukocytes is regulated by TGF-β,” European Journal of Immunology, vol. 41, no. 10, pp. 2955–2965, 2011. View at Publisher · View at Google Scholar · View at Scopus
  61. F. Chalmin, G. Mignot, M. Bruchard et al., “Stat3 and Gfi-1 transcription factors control Th17 cell immunosuppressive activity via the regulation of ectonucleotidase expression,” Immunity, vol. 36, no. 3, pp. 362–373, 2012. View at Publisher · View at Google Scholar · View at Scopus
  62. V. Savic, V. Stefanovic, N. Ardaillou, and R. Ardaillou, “Induction of ecto-5'-nucleotidase of rat cultured mesangial cells by interleukin-1β and tumour necrosis factor-α,” Immunology, vol. 70, no. 3, pp. 321–326, 1990. View at Google Scholar · View at Scopus
  63. S. W. Jackson, T. Hoshi, Y. Wu et al., “Disordered purinergic signaling inhibits pathological angiogenesis in Cd39/Entpd1-null mice,” American Journal of Pathology, vol. 171, no. 4, pp. 1395–1404, 2007. View at Publisher · View at Google Scholar · View at Scopus
  64. X. Sun, Y. Wu, W. Gao et al., “CD39/ENTPD1 expression by CD4+Foxp3+ regulatory T cells promotes hepatic metastatic tumor growth in mice,” Gastroenterology, vol. 139, no. 3, pp. 1030–1040, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. B. M. Künzli, M. I. Bernlochner, S. Rath et al., “Impact of CD39 and purinergic signalling on the growth and metastasis of colorectal cancer,” Purinergic Signalling, vol. 7, no. 2, pp. 231–241, 2011. View at Publisher · View at Google Scholar · View at Scopus
  66. J. Stagg, U. Divisekera, H. Duret et al., “CD73-deficient mice have increased antitumor immunity and are resistant to experimental metastasis,” Cancer Research, vol. 71, no. 8, pp. 2892–2900, 2011. View at Publisher · View at Google Scholar · View at Scopus
  67. L. Wang, J. Fan, L. F. Thompson et al., “CD73 has distinct roles in nonhematopoietic and hematopoietic cells to promote tumor growth in mice,” Journal of Clinical Investigation, vol. 121, no. 6, pp. 2371–2382, 2011. View at Publisher · View at Google Scholar · View at Scopus
  68. D. Jin, J. Fan, L. Wang et al., “CD73 on tumor cells impairs antitumor T-cell responses: a novel mechanism of tumor-induced immune suppression,” Cancer Research, vol. 70, no. 6, pp. 2245–2255, 2010. View at Publisher · View at Google Scholar · View at Scopus
  69. P. A. Beavis, J. Stagg, P. K. Darcy, and M. J. Smyth, “CD73: a potent suppressor of antitumor immune responses,” Trends in Immunology, vol. 33, no. 5, pp. 231–237, 2012. View at Publisher · View at Google Scholar · View at Scopus
  70. R. Leth-Larsen, R. Lund, H. V. Hansen et al., “Metastasis-related plasma membrane proteins of human breast cancer cells identified by comparative quantitative mass spectrometry,” Molecular and Cellular Proteomics, vol. 8, no. 6, pp. 1436–1449, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. X.-R. Wu, X.-S. He, Y.-F. Chen et al., “High expression of CD73 as a poor prognostic biomarker in human colorectal cancer,” Journal of Surgical Oncology, vol. 106, no. 2, pp. 130–137, 2012. View at Publisher · View at Google Scholar · View at Scopus
  72. D. Pulte, R. R. Furman, M. J. Broekman et al., “CD39 expression on T lymphocytes correlates with severity of disease in patients with chronic lymphocytic leukemia,” Clinical Lymphoma, Myeloma and Leukemia, vol. 11, no. 4, pp. 367–372, 2011. View at Publisher · View at Google Scholar · View at Scopus
  73. A. Ohta, E. Gorelik, S. J. Prasad et al., “A2A adenosine receptor protects tumors from antitumor T cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 35, pp. 13132–13137, 2006. View at Publisher · View at Google Scholar · View at Scopus
  74. A. Clayton, S. Al-Taei, J. Webber, M. D. Mason, and Z. Tabi, “Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production,” Journal of Immunology, vol. 187, no. 2, pp. 676–683, 2011. View at Publisher · View at Google Scholar · View at Scopus
  75. C. Cekic, D. Sag, Y. Li, D. Theodorescu, R. M. Strieter, and J. Linden, “Adenosine A2B receptor blockade slows growth of bladder and breast tumors,” Journal of Immunology, vol. 188, no. 1, pp. 198–205, 2012. View at Publisher · View at Google Scholar · View at Scopus
  76. T. Kong, K. A. Westerman, M. Faigle, H. K. Eltzschig, and S. P. Colgan, “HIF-dependent induction of adenosine A2B receptor in hypoxia,” FASEB Journal, vol. 20, no. 13, pp. 2242–2250, 2006. View at Publisher · View at Google Scholar · View at Scopus
  77. S. Merighi, A. Benini, P. Mirandola et al., “Caffeine inhibits adenosine-induced accumulation of hypoxia-inducible factor-1α, vascular endothelial growth factor, and interleukin-8 expression in hypoxic human colon cancer cells,” Molecular Pharmacology, vol. 72, no. 2, pp. 395–406, 2007. View at Publisher · View at Google Scholar · View at Scopus
  78. M. Yang, C. Ma, S. Liu et al., “HIF-dependent induction of adenosine receptor A2B skews human dendritic cells to a Th2-stimulating phenotype under hypoxia,” Immunology and Cell Biology, vol. 88, no. 2, pp. 165–171, 2010. View at Publisher · View at Google Scholar · View at Scopus
  79. E. M. Shevach, “Mechanisms of Foxp3+ T regulatory cell-mediated suppression,” Immunity, vol. 30, no. 5, pp. 636–645, 2009. View at Publisher · View at Google Scholar · View at Scopus
  80. A. M. Wolf, D. Wolf, M. Steurer, G. Gastl, E. Gunsilius, and B. Grubeck-Loebenstein, “Increase of regulatory T cells in the peripheral blood of cancer patients,” Clinical Cancer Research, vol. 9, no. 2, pp. 606–612, 2003. View at Google Scholar · View at Scopus
  81. F. Ghiringhelli, N. Larmonier, E. Schmitt et al., “CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative,” European Journal of Immunology, vol. 34, no. 2, pp. 336–344, 2004. View at Publisher · View at Google Scholar · View at Scopus
  82. S. Ladoire, F. Martin, and F. Ghiringhelli, “Prognostic role of FOXP3+ regulatory T cells infiltrating human carcinomas: the paradox of colorectal cancer,” Cancer Immunology, Immunotherapy, vol. 60, no. 7, pp. 909–918, 2011. View at Publisher · View at Google Scholar · View at Scopus
  83. S. Deaglio, K. M. Dwyer, W. Gao et al., “Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression,” Journal of Experimental Medicine, vol. 204, no. 6, pp. 1257–1265, 2007. View at Publisher · View at Google Scholar · View at Scopus
  84. P. J. Schuler, M. Harasymczuk, B. Schilling, S. Lang, and T. L. Whiteside, “Separation of human CD4+CD39+ T cells by magnetic beads reveals two phenotypically and functionally different subsets,” Journal of Immunological Methods, vol. 369, no. 1-2, pp. 59–68, 2011. View at Publisher · View at Google Scholar · View at Scopus
  85. S. P. Hilchey, J. J. Kobie, M. R. Cochran et al., “Human follicular lymphoma CD39+-infiltrating T cells contribute to adenosine-mediated T cell hyporesponsiveness,” Journal of Immunology, vol. 183, no. 10, pp. 6157–6166, 2009. View at Publisher · View at Google Scholar · View at Scopus
  86. Z. Chen and J. J. O'Shea, “Th17 cells: a new fate for differentiating helper T cells,” Immunologic Research, vol. 41, no. 2, pp. 87–102, 2008. View at Publisher · View at Google Scholar · View at Scopus
  87. W. B. van den Berg and P. Miossec, “IL-17 as a future therapeutic target for rheumatoid arthritis,” Nature Reviews Rheumatology, vol. 5, no. 10, pp. 549–553, 2009. View at Publisher · View at Google Scholar · View at Scopus
  88. Y. Miyahara, K. Odunsi, W. Chen, G. Peng, J. Matsuzaki, and R. F. Wang, “Generation and regulation of human CD4+ IL-17-producing T cells in ovarian cancer,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 40, pp. 15505–15510, 2008. View at Publisher · View at Google Scholar · View at Scopus
  89. K. S. Sfanos, T. C. Bruno, C. H. Maris et al., “Phenotypic analysis of prostate-infiltrating lymphocytes reveals T H17 and Treg skewing,” Clinical Cancer Research, vol. 14, no. 11, pp. 3254–3261, 2008. View at Publisher · View at Google Scholar · View at Scopus
  90. M. F. Su, C. F. Wang, Y. M. Zhao, J. X. Wu, and Y. Zhang, “Expression and clinical significance of IL-17 and IL-21 in patients with acute leukemia,” Journal of Experimental Hematology, vol. 18, no. 5, pp. 1143–1146, 2010. View at Google Scholar · View at Scopus
  91. J. Liu, Y. Duan, X. Cheng et al., “IL-17 is associated with poor prognosis and promotes angiogenesis via stimulating VEGF production of cancer cells in colorectal carcinoma,” Biochemical and Biophysical Research Communications, vol. 407, no. 2, pp. 348–354, 2011. View at Publisher · View at Google Scholar · View at Scopus
  92. J. P. Zhang, J. Yan, J. Xu et al., “Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients,” Journal of Hepatology, vol. 50, no. 5, pp. 980–989, 2009. View at Publisher · View at Google Scholar · View at Scopus
  93. D. He, H. Li, N. Yusuf et al., “IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells,” Journal of Immunology, vol. 184, no. 5, pp. 2281–2288, 2010. View at Publisher · View at Google Scholar · View at Scopus
  94. L. F. Wang, H. C. Chiu, C. J. Hsu, C. Y. Liu, Y. H. Hsueh, and S. C. Miaw, “Epicutaneous sensitization with a protein antigen induces Th17 cells,” Journal of Dermatological Science, vol. 54, no. 3, pp. 192–197, 2009. View at Publisher · View at Google Scholar · View at Scopus
  95. N. Martin-Orozco, P. Muranski, Y. Chung et al., “T helper 17 cells promote cytotoxic T cell activation in tumor immunity,” Immunity, vol. 31, no. 5, pp. 787–798, 2009. View at Publisher · View at Google Scholar · View at Scopus
  96. P. Muranski, A. Boni, P. A. Antony et al., “Tumor-specific Th17-polarized cells eradicate large established melanoma,” Blood, vol. 112, no. 2, pp. 362–373, 2008. View at Publisher · View at Google Scholar · View at Scopus
  97. D. I. Gabrilovich and S. Nagaraj, “Myeloid-derived suppressor cells as regulators of the immune system,” Nature Reviews Immunology, vol. 9, no. 3, pp. 162–174, 2009. View at Publisher · View at Google Scholar · View at Scopus
  98. F. Chalmin, S. Ladoire, G. Mignot et al., “Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells,” Journal of Clinical Investigation, vol. 120, no. 2, pp. 457–471, 2010. View at Publisher · View at Google Scholar · View at Scopus
  99. J. Stagg, P. A. Beavis, U. Divisekera et al., “CD73-Deficient mice are resistant to carcinogenesis,” Cancer Research, vol. 72, no. 9, pp. 2190–2196, 2012. View at Publisher · View at Google Scholar · View at Scopus
  100. M. Michaud, I. Martins, A. Q. Sukkurwala et al., “Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice,” Science, vol. 334, no. 6062, pp. 1573–1577, 2011. View at Publisher · View at Google Scholar · View at Scopus
  101. P. Pellegatti, L. Raffaghello, G. Bianchi, F. Piccardi, V. Pistoia, and F. Di Virgilio, “Increased level of extracellular ATP at tumor sites: in vivo imaging with plasma membrane luciferase,” PLoS ONE, vol. 3, no. 7, Article ID e2599, 2008. View at Publisher · View at Google Scholar · View at Scopus