CD73 as a potential opportunity for cancer immunotherapy

References

• Khalil DN, Smith EL, Brentjens RJ, et al. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol. 2016;13(5):273.
   PubMed Web of Science ®Google Scholar
• Stagg J, Smyth MJ. Extracellular adenosine triphosphate and adenosine in cancer. Oncogene. 2010 Sep 30;29(39):5346–5358. PubMed PMID: 20661219; eng.
   PubMed Web of Science ®Google Scholar
• Smyth MJ, Ngiow SF, Ribas A, et al. Combination cancer immunotherapies tailored to the tumour microenvironment. Nat Rev Clin Oncol. 2016;13(3):143.
   PubMed Web of Science ®Google Scholar
• Pellegatti P, Raffaghello L, Bianchi G, et al. Increased level of extracellular ATP at tumor sites: in vivo imaging with plasma membrane luciferase. PloS one. 2008;3(7):e2599. PubMed PMID: 18612415; PubMed Central PMCID: PMCPmc2440522. eng.
   PubMed Web of Science ®Google Scholar
• Forte G, Sorrentino R, Montinaro A, et al. Inhibition of CD73 improves B cell-mediated anti-tumor immunity in a mouse model of melanoma. J Immunol. 2012 Sep 1;189(5):2226–2233. PubMed PMID: 22826317; PubMed Central PMCID: PMCPmc3442235. eng.
   PubMed Web of Science ®Google Scholar
• Zhang H, Conrad DM, Butler JJ, et al. Adenosine acts through A2 receptors to inhibit IL-2-induced tyrosine phosphorylation of STAT5 in T lymphocytes: role of cyclic adenosine 3ʹ,5ʹ-monophosphate and phosphatases. J Immunol. 2004 Jul 15;173(2):932–944. PubMed PMID: 15240680; eng.
   PubMed Web of Science ®Google Scholar
• Huang S, Apasov S, Koshiba M, et al. Role of A2a extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and expansion. Blood. 1997 Aug 15;90(4):1600–1610. PubMed PMID: 9269779; eng.
   PubMed Web of Science ®Google Scholar
• Ohta A, Ohta A, Madasu M, et al. A2A adenosine receptor may allow expansion of T cells lacking effector functions in extracellular adenosine-rich microenvironments. J Immunol. 2009 Nov 1;183(9):5487–5493. PubMed PMID: 19843934; eng.
   PubMed Web of Science ®Google Scholar
• Ohta A, Gorelik E, Prasad SJ, et al. A2A adenosine receptor protects tumors from antitumor T cells. Proc Nat Acad Sci. 2006;103(35):13132–13137.
   PubMed Web of Science ®Google Scholar
• Spychala J. Tumor-promoting functions of adenosine. Pharmacol Ther. 2000 Aug-Sep;87(2–3):161–173. PubMed PMID: 11007998; eng.
   PubMed Web of Science ®Google Scholar
• Antonioli L, Pacher P, Vizi ES, et al. CD39 and CD73 in immunity and inflammation. Trends Mol Med. 2013;19(6):355–367.
   PubMed Web of Science ®Google Scholar
• Antonioli L, Blandizzi C, Pacher P, et al. Immunity, inflammation and cancer: a leading role for adenosine. Nat Rev Cancer. 2013;13(12):842.
   PubMed Web of Science ®Google Scholar
• Feoktistov I, Biaggioni I. Adenosine A2B receptors. Pharmacol Rev. 1997 Dec;49(4):381–402. PubMed PMID: 9443164; eng.
   PubMed Web of Science ®Google Scholar
• Serra S, Horenstein AL, Vaisitti T, et al. CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death. Blood. 2011;118(23):6141–6152.
   PubMed Web of Science ®Google Scholar
• Sadej R, Spychala J, Skladanowski AC. Expression of ecto-5ʹ-nucleotidase (eN, CD73) in cell lines from various stages of human melanoma. Melanoma Res. 2006 Jun;16(3):213–222. PubMed PMID: 16718268; eng.
   PubMed Web of Science ®Google Scholar
• Bavaresco L, Bernardi A, Braganhol E, et al. The role of ecto-5′-nucleotidase/CD73 in glioma cell line proliferation. Mol Cell Biochem. 2008;319(1–2):61–68.
   PubMed Web of Science ®Google Scholar
• Ludwig HC, Rausch S, Schallock K, et al. Expression of CD 73 (ecto-5ʹ-nucleotidase) in 165 glioblastomas by immunohistochemistry and electronmicroscopic histochemistry. Anticancer Res. 1999 May-Jun;19(3a):1747–1752. PubMed PMID: 10470109; eng.
   PubMed Web of Science ®Google Scholar
• Stella J, Bavaresco L, Braganhol E, et al. Differential ectonucleotidase expression in human bladder cancer cell lines. Urol Oncol. 2010 May-Jun;28(3):260–267. PubMed PMID: 19372055; eng.
   PubMed Web of Science ®Google Scholar
• Spychala J, Lazarowski E, Ostapkowicz A, et al. Role of estrogen receptor in the regulation of ecto-5ʹ-nucleotidase and adenosine in breast cancer. Clin Cancer Res off J Am Assoc Cancer Res. 2004 Jan 15;10(2):708–717. PubMed PMID: 14760094; eng.
   PubMed Web of Science ®Google Scholar
• Kondo T, Nakazawa T, Murata SI, et al. Expression of CD73 and its ecto-5ʹ-nucleotidase activity are elevated in papillary thyroid carcinomas. Histopathology. 2006 Apr;48(5):612–614. PubMed PMID: 16623792; eng.
   PubMed Web of Science ®Google Scholar
• 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 Oct;60(10):1405–1418. PubMed PMID: 21638125; eng.
   PubMed Web of Science ®Google Scholar
• Yang Q, Du J, Zu L. Overexpression of CD73 in prostate cancer is associated with lymph node metastasis. Pathol Oncol Res. 2013 Oct;19(4):811–814. PubMed PMID: 23653114; eng.
   PubMed Web of Science ®Google Scholar
• Eroglu A, Canbolat O, Demirci S, et al. Activities of adenosine deaminase and 5ʹ-nucleotidase in cancerous and noncancerous human colorectal tissues. Med Oncol. 2000 Nov;17(4):319–324. PubMed PMID: 11114712; eng.
   PubMed Web of Science ®Google Scholar
• Fukuda K, Sakakura C, Miyagawa K, et al. Differential gene expression profiles of radioresistant oesophageal cancer cell lines established by continuous fractionated irradiation. Br J Cancer. 2004 Oct 18;91(8):1543–1550. PubMed PMID: 15365572; PubMed Central PMCID: PMCPmc2409931. eng.
   PubMed Web of Science ®Google Scholar
• Durak I, Cetin R, Canbolat O, et al. Adenosine deaminase, 5ʹ-nucleotidase, guanase and cytidine deaminase activities in gastric tissues from patients with gastric cancer. Cancer Lett. 1994 Sep 15;84(2):199–202. PubMed PMID: 8076377; eng.
   PubMed Web of Science ®Google Scholar
• Mandapathil M, Szczepanski MJ, Szajnik M, et al. Increased ectonucleotidase expression and activity in regulatory T cells of patients with head and neck cancer. Clin Cancer Res. 2009 Oct 15;15(20):6348–6357. PubMed PMID: 19825957; PubMed Central PMCID: PMCPmc2763335. eng.
   PubMed Web of Science ®Google Scholar
• 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 Jul 15;187(2):676–683. PubMed PMID: 21677139; eng.
   PubMed Web of Science ®Google Scholar
• Bastid J, Cottalorda-Regairaz A, Alberici G, et al. ENTPD1/CD39 is a promising therapeutic target in oncology. Oncogene. 2013 Apr 4;32(14):1743–1751. PubMed PMID: 22751118; eng.
   PubMed Web of Science ®Google Scholar
• Beavis PA, Stagg J, Darcy PK, et al. CD73: a potent suppressor of antitumor immune responses. Trends Immunol. 2012 May;33(5):231–237. PubMed PMID: 22487321; eng.
   PubMed Web of Science ®Google Scholar
• Antonioli L, Yegutkin GG, Pacher P, et al. Anti-CD73 in cancer immunotherapy: awakening new opportunities. Trends Cancer. 2016;2(2):95–109.
   PubMed Web of Science ®Google Scholar
• Solyom A, Trams E. Enzyme markers in characterization of isolated plasma membranes. Enzyme. 1972;13:329–372.
   PubMedGoogle Scholar
• Misumi Y, Ogata S, Ohkubo K, et al. Primary structure of human placental 5′‐nucleotidase and identification of the glycolipid anchor in the mature form. FEBS J. 1990;191(3):563–569.
   Google Scholar
• Zimmermann H. 5ʹ-Nucleotidase: molecular structure and functional aspects. Biochem J. 1992;285(Pt 2):345.
   PubMedGoogle Scholar
• Sträter N. Ecto-5ʹ-nucleotidase: structure function relationships. Purinergic Signal. 2006;2(2):343.
   PubMedGoogle Scholar
• Eltzschig HK, Köhler D, Eckle T, et al. Central role of Sp1-regulated CD39 in hypoxia/ischemia protection. Blood. 2009;113(1):224–232.
   PubMed Web of Science ®Google Scholar
• Chalmin F, Mignot G, Bruchard M, et al. Stat3 and Gfi-1 transcription factors control Th17 cell immunosuppressive activity via the regulation of ectonucleotidase expression. Immunity. 2012;36(3):362–373.
   PubMed Web of Science ®Google Scholar
• Synnestvedt K, Furuta GT, Comerford KM, et al. Ecto-5′-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia. J Clin Invest. 2002;110(7):993–1002.
   PubMed Web of Science ®Google Scholar
• Regateiro FS, Howie D, Nolan KF, et al. Generation of anti‐inflammatory adenosine byleukocytes is regulated by TGF‐β. Eur J Immunol. 2011;41(10):2955–2965.
   PubMed Web of Science ®Google Scholar
• Niemelä J, Henttinen T, Yegutkin GG, et al. IFN-α induced adenosine production on the endothelium: a mechanism mediated by CD73 (ecto-5′-nucleotidase) up-regulation. J Immunol. 2004;172(3):1646–1653.
   PubMed Web of Science ®Google Scholar
• Spychala J, Wnt KJ. β-catenin signaling target the expression of ecto-5′-nucleotidase and increase extracellular adenosine generation. Exp Cell Res. 2004;296(2):99–108.
   PubMed Web of Science ®Google Scholar
• Gao Z-W, Dong K, Zhang H-Z. The roles of CD73 in cancer. Biomed Res Int. 2014;2014:1–9.
   Google Scholar
• Kitakaze M, Hori M, Morioka T, et al. Infarct size-limiting effect of ischemic preconditioning is blunted by inhibition of 5ʹ-nucleotidase activity and attenuation of adenosine release. Circulation. 1994;89(3):1237–1246.
   PubMed Web of Science ®Google Scholar
• Spychala J, Zimmermann AG, Mitchell BS. Tissue-specific regulation of the ecto-5′-nucleotidase promoter role of the camp response element site in mediating repression by the upstream regulatory region. J Biol Chem. 1999;274(32):22705–22712.
   PubMed Web of Science ®Google Scholar
• Polakis P. Wnt signaling and cancer. Genes Dev. 2000;14(15):1837–1851.
   PubMed Web of Science ®Google Scholar
• Wang H, Lee S, Nigro CL, et al. NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with metastatic site specificity. Br J Cancer. 2012;106(8):1446.
   PubMed Web of Science ®Google Scholar
• Chen W, Jin W, Hardegen N, et al. Conversion of peripheral CD4+ CD25− naive T cells to CD4+ CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3. J Exp Med. 2003;198(12):1875–1886.
   PubMed Web of Science ®Google Scholar
• Savic V, Stefanovic V, Ardaillou N, et al. Induction of ecto-5ʹ-nucleotidase of rat cultured mesangial cells by interleukin-1 beta and tumour necrosis factor-alpha. Immunology. 1990;70(3):321.
   PubMed Web of Science ®Google Scholar
• Jin D, Fan J, Wang L, et al. CD73 on tumor cells impairs antitumor T-cell responses: a novel mechanism of tumor-induced immune suppression. Cancer Res. 2010;70(6):2245–2255.
   PubMed Web of Science ®Google Scholar
• Zhang B. CD73 promotes tumor growth and metastasis. Oncoimmunology. 2012;1(1):67–70.
   PubMed Web of Science ®Google Scholar
• Wang L, Zhou X, Zhou T, et al. Ecto-5′-nucleotidase promotes invasion, migration and adhesion of human breast cancer cells. J Cancer Res Clin Oncol. 2008;134(3):365–372.
   PubMed Web of Science ®Google Scholar
• Dianzani U, Redoglia V, Bragardo M, et al. Co-stimulatory signal delivered by CD73 molecule to human CD45RAhiCD45ROlo (naive) CD8+ T lymphocytes. J Immunol. 1993;151(8):3961–3970.
   PubMed Web of Science ®Google Scholar
• 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(6):1257–1265.
   PubMed Web of Science ®Google Scholar
• 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(4):1225–1232.
   PubMed Web of Science ®Google Scholar
• Jadidi-Niaragh F, Atyabi F, Rastegari A, et al. CD73 specific siRNA loaded chitosan lactate nanoparticles potentiate the antitumor effect of a dendritic cell vaccine in 4T1 breast cancer bearing mice. J Control Release. 2017;246:46–59.
   PubMed Web of Science ®Google Scholar
• Yegutkin GG, Marttila‐Ichihara F, Karikoski M, et al. Altered purinergic signaling in CD73‐deficient mice inhibits tumor progression. Eur J Immunol. 2011;41(5):1231–1241.
   PubMed Web of Science ®Google Scholar
• Thomson L, Ruedi J, Glass A, et al. Production and characterization of monoclonal antibodies to the glycosyl phosphatidylinositol‐anchored lymphocyte differentiation antigen ecto‐5′‐nucleotidase (CD73). HLA. 1990;35(1):9–19.
   Google Scholar
• Rajakumar SV, Lu B, Crikis S, et al. Deficiency or inhibition of CD73 protects in mild kidney ischemia-reperfusion injury. Transplantation. 2010;90(12):1260.
   PubMed Web of Science ®Google Scholar
• Thompson L, Ruedi J, O’Connor R, et al. Ecto-5ʹ-nucleotidase expression during human B cell development. An explanation for the heterogeneity in B lymphocyte ecto-5ʹ-nucleotidase activity in patients with hypogammaglobulinemia. J Immunol. 1986;137(8):2496–2500.
   PubMed Web of Science ®Google Scholar
• Edwards NL, Gelfand EW, Burk L, et al. Distribution of 5ʹ-nucleotidase in human lymphoid tissues. Proc Nat Acad Sci. 1979;76(7):3474–3476.
   PubMed Web of Science ®Google Scholar
• Ma D, Sylwestrowicz T, Granger S, et al. Distribution of terminal deoxynucleotidyl transferase and purine degradative and synthetic enzymes in subpopulations of human thymocytes. J Immunol. 1982;129(4):1430–1435.
   PubMed Web of Science ®Google Scholar
• Resta R, Hooker S, Hansen K, et al. Murine ecto-5ʹ-nucleotidase (CD73): cDNA cloning and tissue distribution. Gene. 1993;133(2):171–177.
   PubMed Web of Science ®Google Scholar
• Thompson LF, Eltzschig HK, Ibla JC, et al. Crucial role for ecto-5′-nucleotidase (CD73) in vascular leakage during hypoxia. J Exp Med. 2004;200(11):1395–1405.
   PubMed Web of Science ®Google Scholar
• Huang Q, Durham NM, Sult E, et al. Levels and enzyme activity of CD73 in primary samples from cancer patients [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18–22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1538. doi:10.1158/1538-7445.AM2015-1538.
   Google Scholar
• Hay C, Sult E, Huang Q, et al. MEDI9447: enhancing anti-tumor immunity by targeting CD73 In the tumor microenvironment [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18–22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 285. doi:10.1158/1538-7445.AM2015-285.
   Google Scholar
• Morello S, Capone M, Sorrentino C, et al. Soluble CD73 as biomarker in patients with metastatic melanoma patients treated with nivolumab. J Transl Med. 2017;15(1):244.
   PubMedGoogle Scholar
• Heuts DP, Weissenborn MJ, Olkhov RV, et al. Crystal structure of a soluble form of human CD73 with ecto‐5′‐nucleotidase activity. Chembiochem. 2012;13(16):2384–2391.
   PubMed Web of Science ®Google Scholar
• Colgan SP, Eltzschig HK, Eckle T, et al. Physiological roles for ecto-5ʹ-nucleotidase (CD73). Purinergic Signal. 2006;2(2):351.
   PubMedGoogle Scholar
• Robson SC, Sévigny J, Zimmermann H. The E-NTPDase family of ectonucleotidases: structure function relationships and pathophysiological significance. Purinergic Signal. 2006;2(2):409.
   PubMedGoogle Scholar
• Heine P, Braun N, Sévigny J, et al. The C‐terminal cysteine‐rich region dictates specific catalytic properties in chimeras of the ectonucleotidases NTPDase1 and NTPDase2. FEBS J. 2001;268(2):364–373.
   Google Scholar
• Fredholm BB, IJzerman AP, Jacobson KA, et al. International union of basic and clinical pharmacology. LXXXI. Nomenclature and classification of adenosine receptors—an update. Pharmacol Rev. 2011;63(1):1–34.
   PubMed Web of Science ®Google Scholar
• Knapp K, Zebisch M, Pippel J, et al. Crystal structure of the human ecto-5′-nucleotidase (CD73): insights into the regulation of purinergic signaling. Structure. 2012;20(12):2161–2173.
   PubMed Web of Science ®Google Scholar
• Takedachi M, Qu D, Ebisuno Y, et al. CD73-generated adenosine restricts lymphocyte migration into draining lymph nodes. J Immunol. 2008;180(9):6288–6296.
   PubMed Web of Science ®Google Scholar
• Mills JH, Thompson LF, Mueller C, et al. CD73 is required for efficient entry of lymphocytes into the central nervous system during experimental autoimmune encephalomyelitis. Proc Nat Acad Sci. 2008;105(27):9325–9330.
   PubMed Web of Science ®Google Scholar
• Resta R, Yamashita Y, Thompson LF. Ecto‐enzyme and signaling functions of lymphocyte CD 7 3. Immunol Rev. 1998;161(1):95–109.
   PubMedGoogle Scholar
• Airas L, Niemelä J, Salmi M, et al. Differential regulation and function of CD73, a glycosyl-phosphatidylinositol–linked 70-kD adhesion molecule, on lymphocytes and endothelial cells. J Cell Biol. 1997;136(2):421–431.
   PubMed Web of Science ®Google Scholar
• Dieckhoff J, Mollenhauer J, Kühl U, et al. The extracellular matrix proteins laminin and fibronectin modify the AMPase activity of 5ʹ‐nucleotidase from chicken gizzard smooth muscle. FEBS Lett. 1986;195(1–2):82–86.
   PubMed Web of Science ®Google Scholar
• Massaia M, Perrin L, Bianchi A, et al. Human T cell activation. Synergy between CD73 (ecto-5ʹ-nucleotidase) and signals delivered through CD3 and CD2 molecules. J Immunol. 1990;145(6):1664–1674.
   PubMed Web of Science ®Google Scholar
• Lokshin A, Raskovalova T, Huang X, et al. Adenosine-mediated inhibition of the cytotoxic activity and cytokine production by activated natural killer cells. Cancer Res. 2006;66(15):7758–7765.
   PubMed Web of Science ®Google Scholar
• Kazemi MH, Raoofi Mohseni S, Hojjat‐Farsangi M, et al. Adenosine and adenosine receptors in the immunopathogenesis and treatment of cancer. J Cell Physiol. 2018;233(3):2032–2057.
   PubMed Web of Science ®Google Scholar
• Shirley DG, Vekaria RM, Sévigny J. Ectonucleotidases in the kidney. Purinergic Signal. 2009;5(4):501.
   PubMed Web of Science ®Google Scholar
• Henttinen T, Jalkanen S, Yegutkin GG. Adherent leukocytes prevent adenosine formation and impair endothelial barrier function by Ecto-5′-nucleotidase/CD73-dependent mechanism. J Biol Chem. 2003;278(27):24888–24895.
   PubMed Web of Science ®Google Scholar
• Mariathasan S, Weiss DS, Newton K, et al. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature. 2006;440(7081):228.
   PubMed Web of Science ®Google Scholar
• Junger WG. Immune cell regulation by autocrine purinergic signalling. Nat Rev Immunol. 2011;11(3):201.
   PubMed Web of Science ®Google Scholar
• Ghiringhelli F, Apetoh L, Tesniere A, et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β–dependent adaptive immunity against tumors. Nat Med. 2009;15(10):1170.
   PubMed Web of Science ®Google Scholar
• Schetinger MRC, Morsch VM, Bonan CD, et al. NTPDase and 5ʹ-nucleotidase activities in physiological and disease conditions: new perspectives for human health. Biofactors. 2007;31(2):77–98.
   PubMed Web of Science ®Google Scholar
• Bastid J, Cottalorda-Regairaz A, Alberici G, et al. ENTPD1/CD39 is a promising therapeutic target in oncology. Oncogene. 2013;32(14):1743.
   PubMed Web of Science ®Google Scholar
• Yegutkin GG. Nucleotide-and nucleoside-converting ectoenzymes: important modulators of purinergic signalling cascade. Biochim Biophys Acta-Mol Cell Res. 2008;1783(5):673–694.
   PubMed Web of Science ®Google Scholar
• St. Hilaire C, Ziegler SG, Markello TC, et al. NT5E mutations and arterial calcifications. N Engl J Med. 2011;364(5):432–442.
   PubMed Web of Science ®Google Scholar
• Leth-Larsen R, Lund R, Hansen HV, et al. Metastasis-related plasma membrane proteins of human breast cancer cells identified by comparative quantitative mass spectrometry. Mol Cell Proteomics. 2009;8(6):1436–1449.
   PubMed Web of Science ®Google Scholar
• Wu XR, He XS, Chen YF, et al. High expression of CD73 as a poor prognostic biomarker in human colorectal cancer. J Surg Oncol. 2012;106(2):130–137.
   PubMed Web of Science ®Google Scholar
• Spychala J, Lazarowski E, Ostapkowicz A, et al. Role of estrogen receptor in the regulation of ecto-5′-nucleotidase and adenosine in breast cancer. Clin Cancer Res. 2004;10(2):708–717.
   PubMed Web of Science ®Google Scholar
• Buisseret L, Pommey S, Allard B, et al. Clinical significance of CD73 in triple-negative breast cancer: multiplex analysis of a phase III clinical trial. Ann Oncol. 2017;29(4):1056–1062.
   Web of Science ®Google Scholar
• Lee H, Lin EC, Liu L, et al. Gene expression profiling of tumor xenografts: in vivo analysis of organ‐specific metastasis. Int J Cancer. 2003;107(4):528–534.
   PubMed Web of Science ®Google Scholar
• Supernat A, Markiewicz A, Welnicka-Jaskiewicz M, et al. CD73 expression as a potential marker of good prognosis in breast carcinoma. Appl Immunohistochem Mol Morphol. 2012;20(2):103–107.
   PubMedGoogle Scholar
• Turcotte M, Spring K, Pommey S, et al. CD73 is associated with poor prognosis in high-grade serous ovarian cancer. Cancer Res. 2015. canres. 3569.2014.
   PubMedGoogle Scholar
• Jadidi-Niaragh F, Yousefi M, Memarian A, et al. Increased frequency of CD8+ and CD4+ regulatory T cells in chronic lymphocytic leukemia: association with disease progression. Cancer Invest. 2013;31(2):121–131.
   PubMed Web of Science ®Google Scholar
• Jadidi-Niaragh F, Ghalamfarsa G, Yousefi M, et al. Regulatory T cells in chronic lymphocytic leukemia: implication for immunotherapeutic interventions. Tumor Biol. 2013;34(4):2031–2039.
   PubMedGoogle Scholar
• Jadidi-Niaragh F, Ghalamfarsa G, Memarian A, et al. Downregulation of IL-17-producing T cells is associated with regulatory T cell expansion and disease progression in chronic lymphocytic leukemia. Tumor Biol. 2013;34(2):929–940.
   PubMedGoogle Scholar
• Coustan-Smith E, Song G, Clark C, et al. New markers for minimal residual disease detection in acute lymphoblastic leukemia. Blood. 2011;117(23):6267–6276.
   PubMed Web of Science ®Google Scholar
• Loi S, Pommey S, Haibe-Kains B, et al. CD73 promotes anthracycline resistance and poor prognosis in triple negative breast cancer. Proc Nat Acad Sci. 2013;110(27):11091–11096.
   PubMed Web of Science ®Google Scholar
• Lu -X-X, Chen Y-T, Feng B, et al. Expression and clinical significance of CD73 and hypoxia-inducible factor-1α in gastric carcinoma. World J Gastroenterol. 2013;19(12):1912.
   PubMed Web of Science ®Google Scholar
• Liu N, Fang XD, Vadis Q. CD73 as a novel prognostic biomarker for human colorectal cancer. J Surg Oncol. 2012;106(7):918–919.
   PubMed Web of Science ®Google Scholar
• Xiong L, Wen Y, Miao X, et al. NT5E and FcGBP as key regulators of TGF-1-induced epithelial–mesenchymal transition (EMT) are associated with tumor progression and survival of patients with gallbladder cancer. Cell Tissue Res. 2014;355(2):365–374.
   PubMed Web of Science ®Google Scholar
• Oh HK, Sin J-I, Choi J, et al. Overexpression of CD73 in epithelial ovarian carcinoma is associated with better prognosis, lower stage, better differentiation and lower regulatory T cell infiltration. J Gynecol Oncol. 2012;23(4):274–281.
   PubMed Web of Science ®Google Scholar
• Wieten E, van der Linden-Schrever B, Sonneveld E, et al. CD73 (5′-nucleotidase) expression has no prognostic value in children with acute lymphoblastic leukemia. Leukemia. 2011;25(8):1374.
   PubMed Web of Science ®Google Scholar
• Zhao S-X, Zhang H-M, Dong S-X, et al. Characteristics and clinical significance of CD73 expression in subtypes of leukemia. Zhongguo shi yan xue ye xue za zhi. 2011;19(5):1141–1144.
   PubMedGoogle Scholar
• Ålgars A, Karikoski M, Yegutkin GG, et al. Different role of CD73 in leukocyte trafficking via blood and lymph vessels. Blood. 2011;117(16):4387–4393.
   PubMed Web of Science ®Google Scholar
• Stagg J, Beavis PA, Divisekera U, et al. CD73-deficient mice are resistant to carcinogenesis. Cancer Res. 2012;72(9):2190–2196.
   PubMed Web of Science ®Google Scholar
• Turcotte M, Allard D, Mittal D, et al. CD73 promotes resistance to HER2/ErbB2 antibody therapy. Cancer Res. 2017. canres. 0707.2017.
   Google Scholar
• Chen L, Diao L, Yang Y, et al. CD38-mediated immunosuppression as a mechanism of tumor cell escape from PD-1/PD-L1 blockade. Cancer Discov. 2018;8(9):1156–1175.
   PubMed Web of Science ®Google Scholar
• Zhi X, Wang Y, Zhou X, et al. RNAi‐mediated CD73 suppression induces apoptosis and cell‐cycle arrest in human breast cancer cells. Cancer Sci. 2010;101(12):2561–2569.
   PubMed Web of Science ®Google Scholar
• Zhou X, Zhi X, Zhou P, et al. Effects of ecto-5ʹ-nucleotidase on human breast cancer cell growth in vitro and in vivo. Oncol Rep. 2007;17(6):1341–1346.
   PubMed Web of Science ®Google Scholar
• Rockenbach L, Bavaresco L, Farias PF, et al. editors. Alterations in the extracellular catabolism of nucleotides are involved in the antiproliferative effect of quercetin in human bladder cancer T24 cells. J Urol Oncol. 2013;31(7):1204–11. Elsevier.
   PubMed Web of Science ®Google Scholar
• 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(8):2892–2900.
   PubMed Web of Science ®Google Scholar
• Wang L, Fan J, Thompson LF, et al. CD73 has distinct roles in nonhematopoietic and hematopoietic cells to promote tumor growth in mice. J Clin Invest. 2011;121(6):2371–2382.
   PubMed Web of Science ®Google Scholar
• Sadej R, Spychala J, Skladanowski A. Ecto-5′-nucleotidase (eN, CD73) is coexpressed with metastasis promoting antigens in human melanoma cells. Nucleosides Nucleotides Nucleic Acids. 2006;25(9–11):1119–1123.
   PubMed Web of Science ®Google Scholar
• Airas L, Niemelä J, Jalkanen S. CD73 engagement promotes lymphocyte binding to endothelial cells via a lymphocyte function-associated antigen-1-dependent mechanism. J Immunol. 2000;165(10):5411–5417.
   PubMed Web of Science ®Google Scholar
• Stagg J, Divisekera U, McLaughlin N, et al. Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis. Proc Nat Acad Sci. 2010;107(4):1547–1552.
   PubMed Web of Science ®Google Scholar
• Richard CL, Tan EY, Blay J. Adenosine upregulates CXCR4 and enhances the proliferative and migratory responses of human carcinoma cells to CXCL12/SDF‐1α. Int J Cancer. 2006;119(9):2044–2053.
   PubMed Web of Science ®Google Scholar
• Rodrigues S, De Wever O, Bruyneel E, et al. Opposing roles of netrin-1 and the dependence receptor DCC in cancer cell invasion, tumor growth and metastasis. Oncogene. 2007;26(38):5615.
   PubMed Web of Science ®Google Scholar
• Mikhailov A, Sokolovskaya A, Yegutkin GG, et al. CD73 participates in cellular multiresistance program and protects against TRAIL-induced apoptosis. J Immunol. 2008;181(1):464–475.
   PubMed Web of Science ®Google Scholar
• Ujházy P, Berleth ES, Pietkiewicz JM, et al. Evidence for the involvement of ecto‐5′‐nucleotidase (CD73) in drug resistance. Int J Cancer. 1996;68(4):493–500.
   PubMed Web of Science ®Google Scholar
• Ghalamfarsa G, Rastegari A, Atyabi F, et al. Anti‐angiogenic effects of CD73‐specific siRNA‐loaded nanoparticles in breast cancer‐bearing mice. J Cell Physiol. 2018;233:7165–7177.
   Web of Science ®Google Scholar
• Allard B, Turcotte M, Spring K, et al. Anti‐CD73 therapy impairs tumor angiogenesis. Int J Cancer. 2014;134(6):1466–1473.
   PubMed Web of Science ®Google Scholar
• Häusler SF, Del Barrio IM, 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(10):1405.
   PubMed Web of Science ®Google Scholar
• Häusler SF, Del Barrio IM, Diessner J, et al. Anti-CD39 and anti-CD73 antibodies A1 and 7G2 improve targeted therapy in ovarian cancer by blocking adenosine-dependent immune evasion. Am J Transl Res. 2014;6(2):129.
   PubMed Web of Science ®Google Scholar
• Stagg J, Smyth M. Extracellular adenosine triphosphate and adenosine in cancer. Oncogene. 2010;29(39):5346.
   PubMed Web of Science ®Google Scholar
• Allard B, Turcotte M, Stagg J. CD73-generated adenosine: orchestrating the tumor-stroma interplay to promote cancer growth. J Biomed Biotechnol. 2012;2012:485156. doi: 10.1155/2012/485156..
   Google Scholar
• Kobie JJ, Shah PR, Yang L, et al. 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. 2006;177(10):6780–6786.
   PubMed Web of Science ®Google Scholar
• Kryczek I, Banerjee M, Cheng P, et al. Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood. 2009;114(6):1141–1149.
   PubMed Web of Science ®Google Scholar
• Jadidi-Niaragh F, Atyabi F, Rastegari A, et al. Downregulation of CD73 in 4T1 breast cancer cells through siRNA-loaded chitosan-lactate nanoparticles. Tumor Biol. 2016;37(6):8403–8412.
   PubMedGoogle Scholar
• Schreiber K, Rowley DA, Riethmüller G, et al. Cancer immunotherapy and preclinical studies: why we are not wasting our time with animal experiments. Hematol/Oncol Clin. 2006;20(3):567–584.
   PubMed Web of Science ®Google Scholar
• Zhang B. Opportunities and challenges for anti-CD73 cancer therapy. Immunotherapy. 2012;4(9):861–865.
   PubMed Web of Science ®Google Scholar
• Allard B, Pommey S, Smyth MJ, et al. Targeting CD73 enhances the antitumor activity of anti-PD-1 and anti-CTLA-4 mAbs. Clin Cancer Res. 2013;19(20):5626–5635.
   PubMed Web of Science ®Google Scholar
• Iannone R, Miele L, Maiolino P, et al. Adenosine limits the therapeutic effectiveness of anti-CTLA4 mAb in a mouse melanoma model. Am J Cancer Res. 2014;4(2):172.
   PubMed Web of Science ®Google Scholar
• Young A, Ngiow SF, Barkauskas DS, et al. Co-inhibition of CD73 and A2AR adenosine signaling improves anti-tumor immune responses. Cancer Cell. 2016;30(3):391–403.
   PubMed Web of Science ®Google Scholar
• Geoghegan JC, Diedrich G, Lu X, et al. editors. Inhibition of CD73 AMP hydrolysis by a therapeutic antibody with a dual, non-competitive mechanism of action. MAbs. 2016;8:454–467. Taylor & Francis.
   Web of Science ®Google Scholar
• Barnhart BC, Sega E, Yamniuk A, et al. A therapeutic antibody that inhibits CD73 activity by dual mechanisms [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16–20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1476.
   Google Scholar
• Hay CM, Sult E, Huang Q, et al. Targeting CD73 in the tumor microenvironment with MEDI9447. Oncoimmunology. 2016;5(8):e1208875.
   PubMed Web of Science ®Google Scholar
• Antonioli L, Novitskiy SV, Sachsenmeier KF, et al. Switching off CD73: a way to boost the activity of conventional and targeted antineoplastic therapies. Drug Discov Today. 2017;22(11):1686–1696.
   PubMed Web of Science ®Google Scholar
• Paoli MG, Augier S, Blemont MR, et al. Discovery and characterization of new original blocking antibodies targeting the CD73 immune checkpoint for cancer immunotherapy [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16–20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2344.
   Google Scholar
• Willingham SB, Ho PY, Hotson A, et al. A2AR antagonism with CPI-444 induces antitumor responses and augments efficacy to anti–PD-(L) 1 and anti–CTLA-4 in preclinical models. Cancer Immunol Res. 2018;6(10):1136–1149.
   PubMed Web of Science ®Google Scholar
• Beavis PA, Milenkovski N, Henderson MA, et al. Adenosine receptor 2A blockade increases the efficacy of anti-PD-1 through enhanced anti-tumor T cell responses. Cancer Immunol Res. 2015 May;3(5):506–17.
   PubMed Web of Science ®Google Scholar
• Allard B, Pommey S, Smyth MJ, et al. Targeting CD73 enhances the antitumor activity of anti-PD-1 and anti-CTLA-4 mAbs. Clin Cancer Res. 2013;19:5626–5635.
   PubMed Web of Science ®Google Scholar