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Review

Targeting adenosine in cancer immunotherapy: a review of recent progress

Pages 527-535 | Received 13 Jan 2017, Accepted 31 Mar 2017, Published online: 27 Apr 2017

References

  • Burnstock G. Introduction to the special issue on purinergic receptors. Adv Exp Med Biol. 2017. [Epub ahead of print].
  • Yegutkin GG. Nucleotide- and nucleoside-converting ectoenzymes: important modulators of purinergic signalling cascade. Biochim Biophys Acta. 2008;1783:673–694.
  • Gallucci S, Matzinger P. Danger signals: SOS to the immune system. Curr Opin Immunol. 2001;13:114–119.
  • Idzko M, Ferrari D, Eltzschig HK. Nucleotide signalling during inflammation. Nature. 2014;509:310–317.
  • Jacob F, Perez Novo C, Bachert C, et al. Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses. Purinergic Signal. 2013;9:285–306.
  • Antonioli L, Colucci R, La Motta C, et al. Adenosine deaminase in the modulation of immune system and its potential as a novel target for treatment of inflammatory disorders. Curr Drug Targets. 2012;13:842–862.
  • Hasko G, Cronstein BN. Adenosine: an endogenous regulator of innate immunity. Trends Immunol. 2004;25:33–39.
  • Ralevic V, Burnstock G. Receptors for purines and pyrimidines. Pharmacol Rev. 1998;50:413–492.
  • Welihinda AA, Kaur M, Greene K, et al. The adenosine metabolite inosine is a functional agonist of the adenosine A2A receptor with a unique signaling bias. Cell Signal. 2016;28:552–560.
  • Hasko G, Sitkovsky MV, Szabo C. Immunomodulatory and neuroprotective effects of inosine. Trends Pharmacol Sci. 2004;25:152–157.
  • Vaupel P, Mayer A. Hypoxia-driven adenosine accumulation: a crucial microenvironmental factor promoting tumor progression. Adv Exp Med Biol. 2016;876:177–183.
  • Borea PA, Gessi S, Merighi S, et al. Adenosine as a multi-signalling guardian angel in human diseases: when, where and how does it exert its protective effects? Trends Pharmacol Sci. 2016;37:419–434.
  • Strater N. Ecto-5ʹ-nucleotidase: structure function relationships. Purinergic Signal. 2006;2:343–350.
  • Allard B, Turcotte M, Stagg J. CD73-generated adenosine: orchestrating the tumor-stroma interplay to promote cancer growth. J Biomed Biotechnol. 2012;2012:485156.
  • Stagg J, Thompson LF, Dwyer KM. Ectonucleotidases in cancer and inflammation. J Biomed Biotechnol. 2012;2012:951423.
  • Aliagas E, Vidal A, Texido L, et al. High expression of ecto-nucleotidases CD39 and CD73 in human endometrial tumors. Mediators Inflamm. 2014;2014:509027.
  • Muller-Haegele S, Muller L, Whiteside TL. Immunoregulatory activity of adenosine and its role in human cancer progression. Expert Rev Clin Immunol. 2014;10:897–914.
  • Ohta A. A metabolic immune checkpoint: adenosine in tumor microenvironment. Front Immunol. 2016;7:109.
  • Ryzhov S, Zaynagetdinov R, Goldstein AE, et al. Effect of A2B adenosine receptor gene ablation on proinflammatory adenosine signaling in mast cells. J Immunol. 2008;180:7212–7220.
  • Zarek PE, Powell JD. Adenosine and anergy. Autoimmunity. 2007;40:425–432.
  • Csoka B, Himer L, Selmeczy Z, et al. Adenosine A2A receptor activation inhibits T helper 1 and T helper 2 cell development and effector function. Faseb J. 2008;22:3491–3499.
  • Cekic C, Linden J. Adenosine A2A receptors intrinsically regulate CD8+ T cells in the tumor microenvironment. Cancer Res. 2014;74:7239–7249.
  • Csoka B, Selmeczy Z, Koscso B, et al. Adenosine promotes alternative macrophage activation via A2A and A2B receptors. Faseb J. 2012;26:376–386.
  • Hasko G, Kuhel DG, Chen JF, et al. Adenosine inhibits IL-12 and TNF-[alpha] production via adenosine A2a receptor-dependent and independent mechanisms. Faseb J. 2000;14:2065–2074.
  • Nemeth ZH, Lutz CS, Csoka B, et al. Adenosine augments IL-10 production by macrophages through an A2B receptor-mediated posttranscriptional mechanism. J Immunol. 2005;175:8260–8270.
  • Csoka B, Koscso B, Toro G, et al. A2B adenosine receptors prevent insulin resistance by inhibiting adipose tissue inflammation via maintaining alternative macrophage activation. Diabetes. 2014;63:850–866.
  • Whiteside TL. The role of regulatory T cells in cancer immunology. Immunotargets Ther. 2015;4:159–171.
  • Mandapathil M, Hilldorfer B, Szczepanski MJ, et al. Generation and accumulation of immunosuppressive adenosine by human CD4+CD25highFOXP3+ regulatory T cells. J Biol Chem. 2010;285:7176–7186.
  • Borsellino G, Kleinewietfeld M, Di Mitri D, et al. Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood. 2007;110:1225–1232.
  • Deaglio S, Dwyer KM, Gao W, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med. 2007;204:1257–1265.
  • Mandapathil M, Szczepanski MJ, Szajnik M, et al. Adenosine and prostaglandin E2 cooperate in the suppression of immune responses mediated by adaptive regulatory T cells. J Biol Chem. 2010;285:27571–27580.
  • Ohta A, Kini R, Ohta A, et al. The development and immunosuppressive functions of CD4(+) CD25(+) FoxP3(+) regulatory T cells are under influence of the adenosine-A2A adenosine receptor pathway. Front Immunol. 2012;3:190.
  • Stagg J, Divisekera U, Duret H, et al. CD73-deficient mice have increased antitumor immunity and are resistant to experimental metastasis. Cancer Res. 2011;71:2892–2900.
  • Mandapathil M, Szczepanski M, Harasymczuk M, et al. CD26 expression and adenosine deaminase activity in regulatory T cells (Treg) and CD4(+) T effector cells in patients with head and neck squamous cell carcinoma. Oncoimmunology. 2012;1:659–669.
  • Hasko G, Kuhel DG, Nemeth ZH, et al. Inosine inhibits inflammatory cytokine production by a posttranscriptional mechanism and protects against endotoxin-induced shock. J Immunol. 2000;164:1013–1019.
  • Marton A, Pacher P, Murthy KG, et al. Anti-inflammatory effects of inosine in human monocytes, neutrophils and epithelial cells in vitro. Int J Mol Med. 2001;8:617–621.
  • Mabley JG, Pacher P, Liaudet L, et al. Inosine reduces inflammation and improves survival in a murine model of colitis. Am J Physiol Gastrointest Liver Physiol. 2003;284:G138–144.
  • Wang D, DuBois RN. The role of anti-inflammatory drugs in colorectal cancer. Annu Rev Med. 2013;64:131–144.
  • Pang LY, Hurst EA, Argyle DJ. Cyclooxygenase-2: a role in cancer stem cell survival and repopulation of cancer cells during therapy. Stem Cells Int. 2016;2016:2048731.
  • Whiteside TL, Jackson EK. Adenosine and prostaglandin e2 production by human inducible regulatory T cells in health and disease. Front Immunol. 2013;4:212.
  • Nielsen JS, Nelson BH. Tumor-infiltrating B cells and T cells: working together to promote patient survival. Oncoimmunology. 2012;1:1623–1625.
  • Minguet S, Huber M, Rosenkranz L, et al. Adenosine and cAMP are potent inhibitors of the NF-kappa B pathway downstream of immunoreceptors. Eur J Immunol. 2005;35:31–41.
  • Saze Z, Schuler PJ, Hong CS, et al. Adenosine production by human B cells and B cell-mediated suppression of activated T cells. Blood. 2013;122:9–18.
  • Figueiro F, Muller L, Funk S, et al. Phenotypic and functional characteristics of CD39high human regulatory B cells (Breg). Oncoimmunology. 2016;5:e1082703.
  • Rittiner JE, Korboukh I, Hull-Ryde EA, et al. AMP is an adenosine A1 receptor agonist. J Biol Chem. 2012;287:5301–5309.
  • Hausler SF, Montalban Del Barrio I, Strohschein J, et al. Ectonucleotidases CD39 and CD73 on OvCA cells are potent adenosine-generating enzymes responsible for adenosine receptor 2A-dependent suppression of T cell function and NK cell cytotoxicity. Cancer Immunol Immunother. 2011;60:1405–1418.
  • Longhi MS, Robson SC, Bernstein SH, et al. Biological functions of ecto-enzymes in regulating extracellular adenosine levels in neoplastic and inflammatory disease states. J Mol Med (Berl). 2013;91:165–172.
  • Allard D, Allard B, Gaudreau PO, et al. CD73-adenosine: a next-generation target in immuno-oncology. Immunotherapy. 2016;8:145–163.
  • Leclerc BG, Charlebois R, Chouinard G, et al. CD73 expression is an independent prognostic factor in prostate cancer. Clin Cancer Res. 2016;22:158–166.
  • Loi S, Pommey S, Haibe-Kains B, et al. CD73 promotes anthracycline resistance and poor prognosis in triple negative breast cancer. Proc Natl Acad Sci U S A. 2013;110:11091–11096.
  • Turcotte M, Spring K, Pommey S, et al. CD73 is associated with poor prognosis in high-grade serous ovarian cancer. Cancer Res. 2015;75:4494–4503.
  • Sitkovsky MV, Hatfield S, Abbott R, et al. Hostile, hypoxia-A2-adenosinergic tumor biology as the next barrier to overcome for tumor immunologists. Cancer Immunol Res. 2014;2:598–605.
  • Beavis PA, Milenkovski N, Stagg J, et al. A2A blockade enhances anti-metastatic immune responses. Oncoimmunology. 2013;2:e26705.
  • Schuler PJ, Saze Z, Hong CS, et al. Human CD4(+) CD39(+) regulatory T cells produce adenosine upon co-expression of surface CD73 or contact with CD73(+) exosomes or CD73(+) cells. Clin Exp Immunol. 2014;177:531–543.
  • Bastid J, Cottalorda-Regairaz A, Alberici G, et al. ENTPD1/CD39 is a promising therapeutic target in oncology. Oncogene. 2013;32:1743–1751.
  • Whiteside TL. Exosomes and tumor-mediated immune suppression. J Clin Invest. 2016;126:1216–1223.
  • Atay S, Godwin AK. Tumor-derived exosomes: A message delivery system for tumor progression. Commun Integr Biol. 2014;7:e28231.
  • Clayton A, Al-Taei S, Webber J, et al. Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production. J Immunol. 2011;187:676–683.
  • Muller L, Mitsuhashi M, Simms P, et al. Tumor-derived exosomes regulate expression of immune function-related genes in human T cell subsets. Sci Rep. 2016;6:20254.
  • Antonioli L, Blandizzi C, Pacher P, et al. Immunity, inflammation and cancer: a leading role for adenosine. Nat Rev Cancer. 2013;13:842–857.
  • Antonioli L, Pacher P, Vizi ES, et al. CD39 and CD73 in immunity and inflammation. Trends Mol Med. 2013;19:355–367.
  • Young A, Mittal D, Stagg J, et al. Targeting cancer-derived adenosine: new therapeutic approaches. Cancer Discov. 2014;4:879–888.
  • Hay CM, Sult E, Huang Q, et al. Targeting CD73 in the tumor microenvironment with MEDI9447. Oncoimmunology. 2016;5:e1208875.
  • Leone RD, Lo YC, Powell JD. A2aR antagonists: next generation checkpoint blockade for cancer immunotherapy. Comput Struct Biotechnol J. 2015;13:265–272.
  • Beavis PA, Divisekera U, Paget C, et al. Blockade of A2A receptors potently suppresses the metastasis of CD73+ tumors. Proc Natl Acad Sci U S A. 2013;110:14711–14716.
  • Stagg J, Divisekera U, McLaughlin N, et al. Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis. Proc Natl Acad Sci U S A. 2010;107:1547–1552.
  • Bonnefoy N, Bastid J, Alberici G, et al. CD39: A complementary target to immune checkpoints to counteract tumor-mediated immunosuppression. Oncoimmunology. 2015;4:e1003015.
  • Cekic C, Sag D, Li Y, et al. Adenosine A2B receptor blockade slows growth of bladder and breast tumors. J Immunol. 2012;188:198–205.
  • Iwatsubo K, Okumura S, Ishikawa Y. Drug therapy aimed at adenylyl cyclase to regulate cyclic nucleotide signaling. Endocr Metab Immune Disord Drug Targets. 2006;6:239–247.
  • Saldou N, Obernolte R, Huber A, et al. Comparison of recombinant human PDE4 isoforms: interaction with substrate and inhibitors. Cell Signal. 1998;10:427–440.
  • Mittal D, Young A, Stannard K, et al. Antimetastatic effects of blocking PD-1 and the adenosine A2A receptor. Cancer Res. 2014;74:3652–3658.
  • Young A, Mittal D, Stannard K, et al. Co-blockade of immune checkpoints and adenosine A2A receptor suppresses metastasis. Oncoimmunology. 2014;3:e958952.

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