{"entity":{"id":"cd73-adenosine","kind":"target","name":"CD73 / adenosine axis","aka":[],"tldr":"CD73 is an enzyme on tumour and immune cells that converts AMP into adenosine, which switches off T and natural killer cells through A2A and A2B receptors. Oleclumab (anti-CD73) with durvalumab slowed progression in a phase 2 lung cancer trial and quemliclustat is in phase 3 in pancreatic cancer, but A2A blockers gave only modest signals and several were dropped.","summary":"CD39 converts extracellular ATP to AMP and CD73 (NT5E) converts AMP to adenosine, which suppresses T and NK cells via A2A/A2B receptors; hypoxia drives the axis. Oleclumab (anti-CD73) plus durvalumab improved PFS in the phase 2 COAST trial (stage III NSCLC) but the phase 3 PACIFIC-9 result is pending; quemliclustat (CD73 inhibitor) is in phase 3 in pancreatic cancer (PRISM-1); A2A antagonists (ciforadenant, etrumadenant, taminadenant) gave modest single-agent signals in RCC and prostate cancer and several were discontinued. CD39 antibodies (TTX-030) and uliledlimab continue in trials.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/5%27-nucleotidase","links":[{"label":"COAST (JCO 2022)","url":"https://doi.org/10.1200/JCO.22.00227"}],"tags":["gap-fill"],"related":[],"cancers":["pancreatic","nsclc","tnbc","rcc","prostate"],"sections":[],"technologies":["checkpoint-inhibitor","monoclonal-antibody"],"targets":[],"drugs":["ak119","mavrostobart","oleclumab","quemliclustat","uliledlimab"],"companies":["astrazeneca","gilead"],"institutions":[],"pathways":["pd1-checkpoint"],"terms":[],"trials":["nct03334617","nct03381274","nct03742102","nct04068610","nct04969315","nct05024097","nct05061550","nct05221840","nct05329766","nct05403385","nct05431270","nct05633667","nct05676931","nct05689853","nct05846867","nct06048133","nct06606847","nct06608927","nct06984588","nct07005336","nct07146230","nct07172802"],"people":[],"bottlenecks":[],"keyPapers":["paper-herbst-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":["Prevalence is not well characterised: CD73 expression is continuous and scored by cutoff-dependent IHC or multiplex assays (NSCLC n=642, Inoue 2017, doi:10.18632/oncotarget.14434; TNBC n=122, Buisseret 2018, doi:10.1093/annonc/mdx730), which report prognostic associations of high expression rather than a positivity rate, and no trial has selected patients on CD73."],"symbol":"NT5E","role":["immune-checkpoint"],"sources":[],"specificity":"immune-microenvironment","distribution":"many-types","specificityNote":"Immune or microenvironment target: its medicines act on immune, stromal or bone cells rather than on the tumour cell (drug mechanisms in the corpus). HPA NT5E: RNA tissue enhanced (cervix 106 nTPM); blood lineage group enriched (B-cells 33 nTPM, T-cells 31 nTPM); high antibody staining in 21 normal tissues; highest cancer staining colorectal cancer (10 of 12 high). Distribution: 5 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Pancreatic ductal adenocarcinoma, Lung cancer (all types), Breast cancer (all types), Renal cell carcinoma, Prostate cancer); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 1 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas NT5E tissue","url":"https://www.proteinatlas.org/ENSG00000135318-NT5E/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"UniProt P21589","url":"https://www.uniprot.org/uniprotkb/P21589/entry","note":"involvement in disease"},{"label":"Open Targets ENSG00000135318 associations","url":"https://platform.opentargets.org/target/ENSG00000135318/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:8021","ensembl":"ENSG00000135318","uniprot":"P21589","entrez":"4907","firstDescribed":1990,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Misumi et al, Eur. J. Biochem, 1990, \"Primary structure of human placental 5'-nucleotidase and identification of the glycolipid anchor in the mature form\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2129526/","biology":"Ecto-5'-nucleotidase anchored by GPI; produces adenosine that binds Gs-coupled A2A/A2B receptors, raising cAMP/PKA in lymphocytes and blunting TCR signalling, cytokine release and cytotoxicity; also promotes Treg and MDSC function.","whereFound":["Pancreatic cancer (high CD73)","NSCLC (especially KRAS/STK11-mutant)","TNBC, ovarian, colorectal cancer","Tregs, MDSCs and endothelium in the microenvironment"],"targetClass":"enzyme","prevalence":[{"cancerId":"metastatic-cancer","pct":"immune","measure":"Immune-cell target (CD73 and adenosine on tumour and immune cells; tumour expression varies and is measured in trials): expressed on immune cells rather than on the tumour, so patient selection rests on the cancer type and, in trials, on PD-L1 or immune biomarkers."}]},"route":"/targets/cd73-adenosine/","neighbours":{"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}],"drug":[{"id":"ak119","kind":"drug","name":"AK119","route":"/drugs/ak119/"},{"id":"mavrostobart","kind":"drug","name":"Mavrostobart","route":"/drugs/mavrostobart/"},{"id":"oleclumab","kind":"drug","name":"Oleclumab","route":"/drugs/oleclumab/"},{"id":"quemliclustat","kind":"drug","name":"Quemliclustat","route":"/drugs/quemliclustat/"},{"id":"uliledlimab","kind":"drug","name":"Uliledlimab","route":"/drugs/uliledlimab/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"},{"id":"gilead","kind":"company","name":"Gilead Sciences (incl. Kite)","route":"/companies/gilead/"}],"pathway":[{"id":"nutrient-competition-tme","kind":"pathway","name":"Nutrient competition & metabolic immunosuppression","route":"/pathways/nutrient-competition-tme/"},{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"}],"trial":[{"id":"nct05221840","kind":"trial","name":"A Global Study to Assess the Effects of Durvalumab With Oleclumab or Durvalumab With Monalizumab Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer","route":"/trials/nct05221840/"},{"id":"nct05024097","kind":"trial","name":"A Phase I-II Study to Test the Safety and Efficacy of PD1 (AB122) and Adenosine Receptor (AB928) Antagonists With Chemotherapy After Short-Course Radiation for","route":"/trials/nct05024097/"},{"id":"nct05846867","kind":"trial","name":"A Phase Ib/II Clinical Study on AK112 Combined or Not Combined With AK119 in pMMR/MSS Colorectal Cancer","route":"/trials/nct05846867/"},{"id":"nct05329766","kind":"trial","name":"A Safety and Efficacy Study of Treatment Combinations With and Without Chemotherapy in Adult Participants With Advanced Upper Gastrointestinal Tract Malignancies","route":"/trials/nct05329766/"},{"id":"nct07172802","kind":"trial","name":"A Study of GI-108, an Anti-CD73-IgG4 Fc-IL-2v Bispecific Fusion Protein, as Monotherapy in Patients With Advanced or Metastatic Solid Tumors","route":"/trials/nct07172802/"},{"id":"nct03742102","kind":"trial","name":"A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer","route":"/trials/nct03742102/"},{"id":"nct07005336","kind":"trial","name":"A Study to Compare Uliledlimab Combined With Sintilimab and Chemotherapy Versus Sintilimab Combined With Chemotherapy in Patients With Previously Untr","route":"/trials/nct07005336/"},{"id":"nct06984588","kind":"trial","name":"A Study to Compare Uliledlimab Combined With Toripalimab, Toripalimab Monotherapy, and Pembrolizumab Monotherapy in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic PD-L1- and CD73- Selected Non-Small Cell Lung Cancer","route":"/trials/nct06984588/"},{"id":"nct06606847","kind":"trial","name":"A Study to Investigate the Effects of Durvalumab With Oleclumab Following Chemoradiation in Participants With Locally Advanced Unresectable Non-Small ","route":"/trials/nct06606847/"},{"id":"nct04068610","kind":"trial","name":"COLUMBIA-1: Novel Oncology Therapies in Combination With Chemotherapy and Bevacizumab as First- Line Therapy in MSS-CRC","route":"/trials/nct04068610/"},{"id":"nct05431270","kind":"trial","name":"Dose Escalation/Expansion Study of Mavrostobart (PT199), an Anti-CD73 mAb, Administered Alone and in Combination With a PD-1 Inhibitor or Chemotherapy","route":"/trials/nct05431270/"},{"id":"nct05061550","kind":"trial","name":"Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer","route":"/trials/nct05061550/"},{"id":"nct03381274","kind":"trial","name":"Oleclumab (MEDI9447) Epidermal Growth Factor Receptor Mutant (EGFRm) Non-small Cell Lung Cancer (NSCLC) Novel Combination Study","route":"/trials/nct03381274/"},{"id":"nct03334617","kind":"trial","name":"Phase II Umbrella Study of Novel Anti-cancer Agents in Participants With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy","route":"/trials/nct03334617/"},{"id":"nct05689853","kind":"trial","name":"Study of AK119 Combined With AK112 in Patients With Advanced Solid Tumors","route":"/trials/nct05689853/"},{"id":"nct06048133","kind":"trial","name":"Study of Gemcitabine, Cisplatin, AB680 and AB122 During First Line Treatment of Advanced Biliary Tract Cancers (QUIC)","route":"/trials/nct06048133/"},{"id":"nct05403385","kind":"trial","name":"Study of Inupadenant (EOS100850) With Chemotherapy as Second Line Treatment for Nonsquamous Non-small Cell Lung Cancer","route":"/trials/nct05403385/"},{"id":"nct05633667","kind":"trial","name":"Study of Novel Treatment Combinations in Patients With Lung Cancer","route":"/trials/nct05633667/"},{"id":"nct06608927","kind":"trial","name":"Study of Quemliclustat and Chemotherapy Versus Placebo and Chemotherapy in Patients With Metastatic Pancreatic Ductal Adenocarcinoma","route":"/trials/nct06608927/"},{"id":"nct05676931","kind":"trial","name":"Study With Various Immunotherapy Treatments in Participants With Lung Cancer","route":"/trials/nct05676931/"},{"id":"nct07146230","kind":"trial","name":"The Selective Personalized Radio-Immunotherapy for Locally Advanced Non-Small Cell Lung Cancer Trial 2","route":"/trials/nct07146230/"},{"id":"nct04969315","kind":"trial","name":"TT-4 and TT-10 as Single Agents and in Combination in Subjects With Advanced Selected Solid Tumors and Pleural Mesothelioma","route":"/trials/nct04969315/"}],"paper":[{"id":"paper-herbst-j-clin-oncol","kind":"paper","name":"COAST: An Open-Label, Phase II, Multidrug Platform Study of Durvalumab Alone or in Combination With Oleclumab or Monalizumab in Patients With Unresectable, Stage III Non-Small-Cell Lung Cancer","route":"/key-papers/paper-herbst-j-clin-oncol/"}],"target":[{"id":"adora2a","kind":"target","name":"Adenosine A2A receptor (ADORA2A)","route":"/targets/adora2a/"},{"id":"entpd1","kind":"target","name":"CD39 (ENTPD1)","route":"/targets/entpd1/"}],"term":[{"id":"checkpoint","kind":"term","name":"Checkpoint (two meanings)","route":"/terms/checkpoint/"}]}}