CD73-adenosine: a next-generation target in immuno-oncology.

Cancer immunotherapy has entered in a new era with the development of first-generation immune checkpoint inhibitors targeting the PD1/PD-L1 and CTLA-4 pathways. In this context, considerable research effort is being deployed to find the next generation of cancer immunotherapeutics. The CD73-adenosine axis constitutes one of the most promising pathways in immuno-oncology. We and others have demonstrated the immunosuppressive role of CD73-adenosine in cancer and established proof-of-concept that the targeted blockade of CD73 or adenosine receptors could effectively promote anti-tumor immunity and enhance the activity of first-generation immune checkpoint blockers. With Phase I clinical trials now underway evaluating anti-CD73 or anti-A2A therapies in cancer patients, we here discuss the fundamental, preclinical and clinical findings related to the role of the CD73-adenosinergic pathway in tumor immunity.

[1]  Deena M. A. Gendoo,et al.  CD73 is associated with poor prognosis in high-grade serous ovarian cancer. , 2015, Cancer research.

[2]  T. Hermanns,et al.  CD73 Predicts Favorable Prognosis in Patients with Nonmuscle-Invasive Urothelial Bladder Cancer , 2015, Disease markers.

[3]  K. Yamaguchi,et al.  Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  C. Viret,et al.  Adenosine receptor signaling: a key to opening the blood–brain door , 2015, Fluids and Barriers of the CNS.

[5]  J. Huang,et al.  Oncogenic G Protein GNAQ Induces Uveal Melanoma and Intravasation in Mice. , 2015, Cancer research.

[6]  F. Saad,et al.  CD73 Expression Is an Independent Prognostic Factor in Prostate Cancer , 2015, Clinical Cancer Research.

[7]  R. Hollingsworth,et al.  Abstract 285: MEDI9447: enhancing anti-tumor immunity by targeting CD73 In the tumor microenvironment , 2015 .

[8]  M. Bynoe,et al.  A2A Adenosine Receptor Regulates the Human Blood-Brain Barrier Permeability , 2015, Molecular Neurobiology.

[9]  C. Müller,et al.  α,β-Methylene-ADP (AOPCP) Derivatives and Analogues: Development of Potent and Selective ecto-5'-Nucleotidase (CD73) Inhibitors. , 2015, Journal of medicinal chemistry.

[10]  Guangming Zhou,et al.  Ecto-5'-nucleotidase expression is associated with the progression of renal cell carcinoma. , 2015, Oncology letters.

[11]  M. Aghaei,et al.  Expression of adenosine receptor subclasses in malignant and adjacent normal human prostate tissues , 2015, The Prostate.

[12]  M. Aghaei,et al.  Activation of A2b adenosine receptor regulates ovarian cancer cell growth: involvement of Bax/Bcl-2 and caspase-3. , 2015, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[13]  Akio Ohta,et al.  Immunological mechanisms of the antitumor effects of supplemental oxygenation , 2015, Science Translational Medicine.

[14]  C. Dinarello,et al.  Cell stress increases ATP release in NLRP3 inflammasome-mediated autoinflammatory diseases, resulting in cytokine imbalance , 2015, Proceedings of the National Academy of Sciences.

[15]  Bin Zhang,et al.  The expression and clinical significance of CD73 molecule in human rectal adenocarcinoma , 2015, Tumor Biology.

[16]  K. Ryan,et al.  p73 engages A2B receptor signalling to prime cancer cells to chemotherapy-induced death , 2015, Oncogene.

[17]  N. Abousamra,et al.  Ectonucleoside triphosphate diphosphohydrolase-1 (E-NTPDase1/CD39) as a new prognostic marker in chronic lymphocytic leukemia , 2015, Leukemia & lymphoma.

[18]  J. Linden,et al.  Myeloid expression of adenosine A2A receptor suppresses T and NK cell responses in the solid tumor microenvironment. , 2014, Cancer research.

[19]  U. Flögel,et al.  Growth and metastasis of B16-F10 melanoma cells is not critically dependent on host CD73 expression in mice , 2014, BMC Cancer.

[20]  S. Jalkanen,et al.  Early Prediction of Persistent Organ Failure by Soluble CD73 in Patients With Acute Pancreatitis* , 2014, Critical care medicine.

[21]  M. Trincavelli,et al.  Modulation of A1 and A2B adenosine receptor activity: a new strategy to sensitise glioblastoma stem cells to chemotherapy , 2014, Cell Death and Disease.

[22]  S. Mehrotra,et al.  Reducing CD73 expression by IL1β-Programmed Th17 cells improves immunotherapeutic control of tumors. , 2014, Cancer research.

[23]  J. Sundberg,et al.  Juxta-articular joint-capsule mineralization in CD73 deficient mice: Similarities to patients with NT5E mutations , 2014, Cell cycle.

[24]  S. Jalkanen,et al.  Adenosine Inhibits Tumor Cell Invasion via Receptor-Independent Mechanisms , 2014, Molecular Cancer Research.

[25]  M. Smyth,et al.  Antimetastatic effects of blocking PD-1 and the adenosine A2A receptor. , 2014, Cancer research.

[26]  Martin Turcotte,et al.  Targeting CD73 and downstream adenosine receptor signaling in triple-negative breast cancer , 2014, Expert opinion on therapeutic targets.

[27]  A. Ohta,et al.  Hostile, Hypoxia–A2-Adenosinergic Tumor Biology as the Next Barrier to Overcome for Tumor Immunologists , 2014, Cancer Immunology Research.

[28]  J. Dranoff,et al.  NT5E Mutations That Cause Human Disease Are Associated with Intracellular Mistrafficking of NT5E Protein , 2014, PloS one.

[29]  Luzhe Sun,et al.  Differential impact of adenosine nucleotides released by osteocytes on breast cancer growth and bone metastasis , 2014, Oncogene.

[30]  Hong Liao,et al.  The HIF-2alpha dependent induction of PAP and adenosine synthesis regulates glioblastoma stem cell function through the A2B adenosine receptor. , 2014, The international journal of biochemistry & cell biology.

[31]  M. Tsukimoto,et al.  Adenosine A2B receptor antagonist PSB603 suppresses tumor growth and metastasis by inhibiting induction of regulatory T cells , 2014 .

[32]  Kathleen M Spring,et al.  Anti‐CD73 therapy impairs tumor angiogenesis , 2014, International journal of cancer.

[33]  P. Maiolino,et al.  Adenosine limits the therapeutic effectiveness of anti-CTLA4 mAb in a mouse melanoma model. , 2014, American journal of cancer research.

[34]  S. Jalkanen,et al.  The effect of intravenous interferon-beta-1a (FP-1201) on lung CD73 expression and on acute respiratory distress syndrome mortality: an open-label study. , 2014, The Lancet. Respiratory medicine.

[35]  A. Składanowski,et al.  Inhibition of CD73 stimulates the migration and invasion of B16F10 melanoma cells in vitro, but results in impaired angiogenesis and reduced melanoma growth in vivo. , 2014, Oncology reports.

[36]  H. Zimmermann,et al.  A new, sensitive ecto-5'-nucleotidase assay for compound screening. , 2014, Analytical biochemistry.

[37]  J. Wischhusen,et al.  Anti-CD39 and anti-CD73 antibodies A1 and 7G2 improve targeted therapy in ovarian cancer by blocking adenosine-dependent immune evasion. , 2014, American journal of translational research.

[38]  G. Kroemer,et al.  Autophagy in non-small cell lung carcinogenesis , 2014, Autophagy.

[39]  P. Hwu,et al.  IL-2 therapy promotes suppressive ICOS+ Treg expansion in melanoma patients. , 2014, The Journal of clinical investigation.

[40]  X. Miao,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 , 2013, Cell and Tissue Research.

[41]  P. Maiolino,et al.  Blockade of A2b adenosine receptor reduces tumor growth and immune suppression mediated by myeloid-derived suppressor cells in a mouse model of melanoma. , 2013, Neoplasia.

[42]  J. Bajorath,et al.  Identification of sulfonic acids as efficient ecto-5'-nucleotidase inhibitors. , 2013, European journal of medicinal chemistry.

[43]  J. Linden,et al.  Extracellular adenosine regulates naive T cell development and peripheral maintenance , 2013, The Journal of experimental medicine.

[44]  L. Antonioli,et al.  Immunity, inflammation and cancer: a leading role for adenosine , 2013, Nature Reviews Cancer.

[45]  J. Wolchok,et al.  Indoleamine 2,3-dioxygenase is a critical resistance mechanism in anti-tumor T cell immunotherapy targeting CTLA-4 , 2013, Journal of Immunotherapy for Cancer.

[46]  Eva C. Arnspang,et al.  Anti-Human CD73 Monoclonal Antibody Inhibits Metastasis Formation in Human Breast Cancer by Inducing Clustering and Internalization of CD73 Expressed on the Surface of Cancer Cells , 2013, The Journal of Immunology.

[47]  M. Quinn,et al.  Impaired Th1 immunity in ovarian cancer patients is mediated by TNFR2+ Tregs within the tumor microenvironment. , 2013, Clinical immunology.

[48]  X. Qu,et al.  Synergy between the ectoenzymes CD39 and CD73 contributes to adenosinergic immunosuppression in human malignant gliomas. , 2013, Neuro-oncology.

[49]  M. Smyth,et al.  Targeting CD73 Enhances the Antitumor Activity of Anti-PD-1 and Anti-CTLA-4 mAbs , 2013, Clinical Cancer Research.

[50]  M. Smyth,et al.  Blockade of A2A receptors potently suppresses the metastasis of CD73+ tumors , 2013, Proceedings of the National Academy of Sciences.

[51]  S. Antonia,et al.  Antagonism of adenosine A2A receptor expressed by lung adenocarcinoma tumor cells and cancer associated fibroblasts inhibits their growth , 2013, Cancer biology & therapy.

[52]  J. Wolchok,et al.  Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4 , 2013, The Journal of experimental medicine.

[53]  S. Loi,et al.  CD73 promotes anthracycline resistance and poor prognosis in triple negative breast cancer , 2013, Proceedings of the National Academy of Sciences.

[54]  G. Freeman,et al.  Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. , 2013, Cancer research.

[55]  E. Vizi,et al.  CD39 and CD73 in immunity and inflammation. , 2013, Trends in molecular medicine.

[56]  Carol L. Williams,et al.  An Adenosine-Mediated Signaling Pathway Suppresses Prenylation of the GTPase Rap1B and Promotes Cell Scattering , 2013, Science Signaling.

[57]  T. Palmer,et al.  Extracellular adenosine sensing-a metabolic cell death priming mechanism downstream of p53. , 2013, Molecular cell.

[58]  Jun Du,et al.  Overexpression of CD73 in Prostate Cancer is Associated with Lymph Node Metastasis , 2013, Pathology & Oncology Research.

[59]  D. Lad,et al.  Regulatory T-cells in B-cell chronic lymphocytic leukemia: their role in disease progression and autoimmune cytopenias , 2013, Leukemia & lymphoma.

[60]  J. Ferlay,et al.  Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. , 2013, European journal of cancer.

[61]  Yitian Chen,et al.  Expression and clinical significance of CD73 and hypoxia-inducible factor-1α in gastric carcinoma. , 2013, World journal of gastroenterology.

[62]  Steffen Jung,et al.  Recruitment of beneficial M2 macrophages to injured spinal cord is orchestrated by remote brain choroid plexus. , 2013, Immunity.

[63]  Z. Ou,et al.  Ecto-5′-nucleotidase (CD73) promotes tumor angiogenesis , 2013, Clinical & Experimental Metastasis.

[64]  Sridhar Ramaswamy,et al.  Identification of a pharmacologically tractable Fra-1/ADORA2B axis promoting breast cancer metastasis , 2013, Proceedings of the National Academy of Sciences.

[65]  R. Rosenquist,et al.  Prognostic markers and their clinical applicability in chronic lymphocytic leukemia: where do we stand? , 2013, Leukemia & lymphoma.

[66]  P. Casanello,et al.  5′‐ectonucleotidase mediates multiple‐drug resistance in glioblastoma multiforme cells , 2013, Journal of cellular physiology.

[67]  S. O'toole,et al.  Therapeutic targets in triple negative breast cancer , 2013, Journal of Clinical Pathology.

[68]  R. Minter,et al.  Combining phenotypic and proteomic approaches to identify membrane targets in a ‘triple negative’ breast cancer cell type , 2013, Molecular Cancer.

[69]  K. Brodsky,et al.  Transcriptional control of adenosine signaling by hypoxia-inducible transcription factors during ischemic or inflammatory disease , 2013, Journal of Molecular Medicine.

[70]  J. Stagg,et al.  Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects , 2013, Therapeutic advances in medical oncology.

[71]  A. Składanowski,et al.  Dual, enzymatic and non-enzymatic, function of ecto-5'-nucleotidase (eN, CD73) in migration and invasion of A375 melanoma cells. , 2012, Acta biochimica Polonica.

[72]  L. Yin,et al.  Potential prognostic biomarker CD73 regulates epidermal growth factor receptor expression in human breast cancer , 2012, IUBMB life.

[73]  Jiang-Fan Chen,et al.  Genetic inactivation of the adenosine A2A receptor exacerbates brain damage in mice with experimental autoimmune encephalomyelitis , 2012, Journal of neurochemistry.

[74]  Jung-Hye Choi,et al.  Overexpression of CD73 in epithelial ovarian carcinoma is associated with better prognosis, lower stage, better differentiation and lower regulatory T cell infiltration , 2012, Journal of gynecologic oncology.

[75]  I. Adcock,et al.  Inhibition of CD73 Improves B Cell-Mediated Anti-Tumor Immunity in a Mouse Model of Melanoma , 2012, The Journal of Immunology.

[76]  Leah M. Alabanza,et al.  Extracellular adenosine signaling induces CX3CL1 expression in the brain to promote experimental autoimmune encephalomyelitis , 2012, Journal of Neuroinflammation.

[77]  Xiaojian Wu,et al.  High expression of CD73 as a poor prognostic biomarker in human colorectal cancer , 2012, Journal of surgical oncology.

[78]  F. Di Virgilio,et al.  The P2X7 receptor is a key modulator of aerobic glycolysis , 2012, Cell Death and Disease.

[79]  J. Bajorath,et al.  Virtual screening identifies novel sulfonamide inhibitors of ecto-5'-nucleotidase. , 2012, Journal of medicinal chemistry.

[80]  M. Horton,et al.  Enhancement of tumor immunotherapy by deletion of the A2A adenosine receptor , 2012, Cancer Immunology, Immunotherapy.

[81]  A. Thompson,et al.  NT5E CpG island methylation is a favourable breast cancer biomarker , 2012, British Journal of Cancer.

[82]  H. Haller,et al.  Autoimmunity in CD73/Ecto-5′-Nucleotidase Deficient Mice Induces Renal Injury , 2012, PloS one.

[83]  A. Möller,et al.  CD73-deficient mice are resistant to carcinogenesis. , 2012, Cancer research.

[84]  A. Thompson,et al.  NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with metastatic site specificity , 2012, British Journal of Cancer.

[85]  P. Czapiewski,et al.  CD73 Expression as a Potential Marker of Good Prognosis in Breast Carcinoma , 2012, Applied immunohistochemistry & molecular morphology : AIMM.

[86]  M. Hyman,et al.  Tissue-Resident Ecto-5′ Nucleotidase (CD73) Regulates Leukocyte Trafficking in the Ischemic Brain , 2012, The Journal of Immunology.

[87]  R. Strieter,et al.  Adenosine A2B Receptor Blockade Slows Growth of Bladder and Breast Tumors , 2012, The Journal of Immunology.

[88]  D. Rossi,et al.  CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death. , 2011, Blood.

[89]  M. Bynoe,et al.  Adenosine Receptor Signaling Modulates Permeability of the Blood–Brain Barrier , 2011, The Journal of Neuroscience.

[90]  O. Carpén,et al.  EGFR gene copy number assessment from areas with highest EGFR expression predicts response to anti-EGFR therapy in colorectal cancer , 2011, British Journal of Cancer.

[91]  Elaine Coustan-Smith,et al.  New markers for minimal residual disease detection in acute lymphoblastic leukemia. , 2011, Blood.

[92]  K. Klotz,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 , 2011, Cancer Immunology, Immunotherapy.

[93]  T. Curiel,et al.  CD73 has distinct roles in nonhematopoietic and hematopoietic cells to promote tumor growth in mice. , 2011, The Journal of clinical investigation.

[94]  S. Jalkanen,et al.  Altered purinergic signaling in CD73‐deficient mice inhibits tumor progression , 2011, European journal of immunology.

[95]  S. Jalkanen,et al.  Different role of CD73 in leukocyte trafficking via blood and lymph vessels. , 2011, Blood.

[96]  C. Perou,et al.  The prognostic contribution of clinical breast cancer subtype, age, and race among patients with breast cancer brain metastases , 2011, Cancer.

[97]  M. Smyth,et al.  CD73-deficient mice have increased antitumor immunity and are resistant to experimental metastasis. , 2011, Cancer research.

[98]  S. Loi,et al.  Anti–ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti–PD-1 or anti-CD137 mAb therapy , 2011, Proceedings of the National Academy of Sciences.

[99]  P. Couraud,et al.  Human brain endothelial cells are responsive to adenosine receptor activation , 2011, Purinergic Signalling.

[100]  T. Markello,et al.  NT5E mutations and arterial calcifications. , 2011, The New England journal of medicine.

[101]  J. Minna,et al.  Knockdown of Oncogenic KRAS in Non–Small Cell Lung Cancers Suppresses Tumor Growth and Sensitizes Tumor Cells to Targeted Therapy , 2011, Molecular Cancer Therapeutics.

[102]  L. Yin,et al.  RNAi‐mediated CD73 suppression induces apoptosis and cell‐cycle arrest in human breast cancer cells , 2010, Cancer science.

[103]  A. Luini,et al.  Prognosis and adjuvant treatment effects in selected breast cancer subtypes of very young women (<35 years) with operable breast cancer. , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[104]  Bin Zhang.  CD73: a novel target for cancer immunotherapy. , 2010, Cancer research.

[105]  T. Whiteside,et al.  Adenosine and Prostaglandin E2 Cooperate in the Suppression of Immune Responses Mediated by Adaptive Regulatory T Cells* , 2010, The Journal of Biological Chemistry.

[106]  G. Müller,et al.  Transfer of the glycosylphosphatidylinositol‐anchored 5′‐nucleotidase CD73 from adiposomes into rat adipocytes stimulates lipid synthesis , 2010, British journal of pharmacology.

[107]  J. Sévigny,et al.  High expression and activity of ecto-5′-nucleotidase/CD73 in the male murine reproductive tract , 2010, Histochemistry and Cell Biology.

[108]  T. Curiel,et al.  CD73 on tumor cells impairs antitumor T-cell responses: a novel mechanism of tumor-induced immune suppression. , 2010, Cancer research.

[109]  J. Bajorath,et al.  Development of potent and selective inhibitors of ecto-5'-nucleotidase based on an anthraquinone scaffold. , 2010, Journal of medicinal chemistry.

[110]  Huiqin Xu,et al.  Chronic caffeine treatment attenuates experimental autoimmune encephalomyelitis induced by guinea pig spinal cord homogenates in Wistar rats , 2010, Brain Research.

[111]  M. Smyth,et al.  Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis , 2010, Proceedings of the National Academy of Sciences.

[112]  Michael R. Elliott,et al.  Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance , 2009, Nature.

[113]  P. Schellhammer,et al.  Integrated data from 2 randomized, double‐blind, placebo‐controlled, phase 3 trials of active cellular immunotherapy with sipuleucel‐T in advanced prostate cancer , 2009, Cancer.

[114]  A. Jemal,et al.  Cancer Statistics, 2009 , 2009, CA: a cancer journal for clinicians.

[115]  S. Narod,et al.  Pattern of metastatic spread in triple-negative breast cancer , 2009, Breast Cancer Research and Treatment.

[116]  S. Jalkanen,et al.  IFN‐β regulates CD73 and adenosine expression at the blood–brain barrier , 2008, European journal of immunology.

[117]  D. Carbone,et al.  Host A(2B) adenosine receptors promote carcinoma growth. , 2008, Neoplasia.

[118]  A. Delgado-Cañedo,et al.  The role of ecto-5′-nucleotidase/CD73 in glioma cell line proliferation , 2008, Molecular and Cellular Biochemistry.

[119]  S. Jalkanen,et al.  CD73 is required for efficient entry of lymphocytes into the central nervous system during experimental autoimmune encephalomyelitis , 2008, Proceedings of the National Academy of Sciences.

[120]  L. Chiriboga,et al.  Ecto‐5′‐nucleotidase (CD73) ‐mediated extracellular adenosine production plays a critical role in hepatic fibrosis , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[121]  John T. Wei,et al.  Quality of life and satisfaction with outcome among prostate-cancer survivors. , 2008, The New England journal of medicine.

[122]  K. Hess,et al.  Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[123]  Z. Ou,et al.  Ecto-5′-nucleotidase promotes invasion, migration and adhesion of human breast cancer cells , 2008, Journal of Cancer Research and Clinical Oncology.

[124]  A. Bernardi,et al.  Ecto-5'-nucleotidase/CD73 inhibition by quercetin in the human U138MG glioma cell line. , 2007, Biochimica et biophysica acta.

[125]  S. Narod,et al.  Triple-Negative Breast Cancer: Clinical Features and Patterns of Recurrence , 2007, Clinical Cancer Research.

[126]  Z. Ou,et al.  RNA interference of ecto-5′-nucleotidase (CD73) inhibits human breast cancer cell growth and invasion , 2007, Clinical & Experimental Metastasis.

[127]  V. Kuchroo,et al.  Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression , 2007, The Journal of experimental medicine.

[128]  Z. Ou,et al.  Effects of ecto-5'-nucleotidase on human breast cancer cell growth in vitro and in vivo. , 2007, Oncology reports.

[129]  Manuel Hidalgo,et al.  Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[130]  R. Cress,et al.  Descriptive analysis of estrogen receptor (ER)‐negative, progesterone receptor (PR)‐negative, and HER2‐negative invasive breast cancer, the so‐called triple‐negative phenotype , 2007, Cancer.

[131]  C. Ledent,et al.  Cardioprotection by Ecto-5′-Nucleotidase (CD73) and A2B Adenosine Receptors , 2007, Circulation.

[132]  H. Osswald,et al.  Protective role of ecto-5'-nucleotidase (CD73) in renal ischemia. , 2007, Journal of the American Society of Nephrology : JASN.

[133]  Elisa Rossi,et al.  Gene expression profile of ovarian serous papillary carcinomas: identification of metastasis-associated genes. , 2007, American journal of obstetrics and gynecology.

[134]  H. Kettenmann,et al.  A1 adenosine receptors in microglia control glioblastoma-host interaction. , 2006, Cancer research.

[135]  Koji Yoshimoto,et al.  Primary Glioblastomas Express Mesenchymal Stem-Like Properties , 2006, Molecular Cancer Research.

[136]  A. Ohta,et al.  A2A adenosine receptor protects tumors from antitumor T cells , 2006, Proceedings of the National Academy of Sciences.

[137]  P. Schellhammer,et al.  Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[138]  C. Perou,et al.  Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. , 2006, JAMA.

[139]  A. Składanowski,et al.  Ecto-5′-Nucleotidase (eN, CD73) is Coexpressed with Metastasis Promoting Antigens in Human Melanoma Cells , 2006, Nucleosides, nucleotides & nucleic acids.

[140]  A. Składanowski,et al.  Expression of ecto-5′-nucleotidase (eN, CD73) in cell lines from various stages of human melanoma , 2006, Melanoma research.

[141]  A. Lièvre,et al.  KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. , 2006, Cancer research.

[142]  David M. Conrad,et al.  Adenosine-induced apoptosis in EL-4 thymoma cells is caspase-independent and mediated through a non-classical adenosine receptor. , 2005, Experimental and molecular pathology.

[143]  E. Vizi,et al.  Adenosine receptor signaling in the brain immune system. , 2005, Trends in pharmacological sciences.

[144]  S. Colgan,et al.  Crucial Role for Ecto-5′-Nucleotidase (CD73) in Vascular Leakage during Hypoxia , 2004, The Journal of experimental medicine.

[145]  K. Ley,et al.  Targeted Disruption of cd73/Ecto-5′-Nucleotidase Alters Thromboregulation and Augments Vascular Inflammatory Response , 2004, Circulation research.

[146]  C. Deng,et al.  Impairment of tubuloglomerular feedback regulation of GFR in ecto-5'-nucleotidase/CD73-deficient mice. , 2004, The Journal of clinical investigation.

[147]  A. Gown,et al.  Immunohistochemical and Clinical Characterization of the Basal-Like Subtype of Invasive Breast Carcinoma , 2004, Clinical Cancer Research.

[148]  C. Power,et al.  A1 Adenosine Receptor Upregulation and Activation Attenuates Neuroinflammation and Demyelination in a Model of Multiple Sclerosis , 2004, The Journal of Neuroscience.

[149]  B. Mitchell,et al.  Role of Estrogen Receptor in the Regulation of Ecto-5′-Nucleotidase and Adenosine in Breast Cancer , 2004, Clinical Cancer Research.

[150]  A. Scaloni,et al.  Biochemical and mass spectrometric characterization of soluble ecto-5'-nucleotidase from bull seminal plasma. , 2003, The Biochemical journal.

[151]  S. Colgan,et al.  Ecto-5'-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia. , 2002, The Journal of clinical investigation.

[152]  A. Gerbes,et al.  [Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage]. , 2002, Zeitschrift fur Gastroenterologie.

[153]  Christian A. Rees,et al.  Molecular portraits of human breast tumours , 2000, Nature.

[154]  M. Peyot,et al.  Extracellular adenosine induces apoptosis of human arterial smooth muscle cells via A(2b)-purinoceptor. , 2000, Circulation research.

[155]  F. Bruckner,et al.  5'-Nucleotidase as a marker of both general and local inflammation in rheumatoid arthritis patients. , 1999, Rheumatology.

[156]  C. Taylor,et al.  Neutrophil-derived 5′-Adenosine Monophosphate Promotes Endothelial Barrier Function via CD73-mediated Conversion to Adenosine and Endothelial A2B Receptor Activation , 1998, The Journal of experimental medicine.

[157]  J. Blay,et al.  The extracellular fluid of solid carcinomas contains immunosuppressive concentrations of adenosine. , 1997, Cancer research.

[158]  B. Williams,et al.  Adenosine acts through a novel extracellular receptor to inhibit granule exocytosis by natural killer cells. , 1997, Biochemical and biophysical research communications.

[159]  J. Blay,et al.  Adenosine as a possible inhibitor of killer T‐cell activation in the microenvironment of solid tumours , 1994, International journal of cancer.

[160]  J. Blay,et al.  2-Chloroadenosine inhibits the MHC-unrestricted cytolytic activity of anti-CD3-activated killer cells: evidence for the involvement of a non-A1/A2 cell-surface adenosine receptor. , 1994, Cellular immunology.

[161]  J. Blay,et al.  Adenosine inhibits the adhesion of anti-CD3-activated killer lymphocytes to adenocarcinoma cells through an A3 receptor. , 1994, Cancer research.

[162]  J. Luzio,et al.  Characterization of different molecular forms of 5'-nucleotidase in normal serum and in serum from cholestatic patients and bile-duct-ligated rats. , 1984, The Biochemical journal.

[163]  Ján.  Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer , 2015 .

[164]  S. Kojima,et al.  Adenosine A(2B) receptor antagonist PSB603 suppresses tumor growth and metastasis by inhibiting induction of regulatory T cells. , 2014, Journal of Toxicological Sciences.

[165]  R. Nussbaum,et al.  NT5E mutations and arterial calcifications. , 2011, The New England journal of medicine.

[166]  M. Sitkovsky,et al.  Role of A2a extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and expansion. , 1997, Blood.

[167]  A. Lucas,et al.  Production and characterization of monoclonal antibodies to the glycosyl phosphatidylinositol-anchored lymphocyte differentiation antigen ecto-5'-nucleotidase (CD73). , 1990, Tissue antigens.

[168]  N. Dubrawsky.  Cancer statistics , 1989, CA: a cancer journal for clinicians.