# CD73 / adenosine axis

Source: https://onco.cc/targets/cd73-adenosine/  
OnCo record `cd73-adenosine` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Target
- Last checked: 2026-09-08
- Tags: gap-fill
- Symbol: NT5E
- Class: enzyme
- 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.
- Where found: Pancreatic cancer (high CD73); NSCLC (especially KRAS/STK11-mutant); TNBC, ovarian, colorectal cancer; Tregs, MDSCs and endothelium in the microenvironment

## 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/5%27-nucleotidase
- COAST (JCO 2022): https://doi.org/10.1200/JCO.22.00227

## Connected records

- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/)
- drugs: [AK119](https://onco.cc/drugs/ak119/), [Mavrostobart](https://onco.cc/drugs/mavrostobart/), [Oleclumab](https://onco.cc/drugs/oleclumab/), [Quemliclustat](https://onco.cc/drugs/quemliclustat/), [Uliledlimab](https://onco.cc/drugs/uliledlimab/)
- companies: [AstraZeneca](https://onco.cc/companies/astrazeneca/), [Gilead Sciences (incl. Kite)](https://onco.cc/companies/gilead/)
- pathways: [Nutrient competition & metabolic immunosuppression](https://onco.cc/pathways/nutrient-competition-tme/), [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/)
- trials: [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](https://onco.cc/trials/nct05221840/), [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](https://onco.cc/trials/nct05024097/), [A Phase Ib/II Clinical Study on AK112 Combined or Not Combined With AK119 in pMMR/MSS Colorectal Cancer](https://onco.cc/trials/nct05846867/), [A Safety and Efficacy Study of Treatment Combinations With and Without Chemotherapy in Adult Participants With Advanced Upper Gastrointestinal Tract Malignancies](https://onco.cc/trials/nct05329766/), [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](https://onco.cc/trials/nct07172802/), [A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer](https://onco.cc/trials/nct03742102/), [A Study to Compare Uliledlimab Combined With Sintilimab and Chemotherapy Versus Sintilimab Combined With Chemotherapy in Patients With Previously Untr](https://onco.cc/trials/nct07005336/), [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](https://onco.cc/trials/nct06984588/), [A Study to Investigate the Effects of Durvalumab With Oleclumab Following Chemoradiation in Participants With Locally Advanced Unresectable Non-Small ](https://onco.cc/trials/nct06606847/), [COLUMBIA-1: Novel Oncology Therapies in Combination With Chemotherapy and Bevacizumab as First- Line Therapy in MSS-CRC](https://onco.cc/trials/nct04068610/), [Dose Escalation/Expansion Study of Mavrostobart (PT199), an Anti-CD73 mAb, Administered Alone and in Combination With a PD-1 Inhibitor or Chemotherapy](https://onco.cc/trials/nct05431270/), [Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer](https://onco.cc/trials/nct05061550/), [Oleclumab (MEDI9447) Epidermal Growth Factor Receptor Mutant (EGFRm) Non-small Cell Lung Cancer (NSCLC) Novel Combination Study](https://onco.cc/trials/nct03381274/), [Phase II Umbrella Study of Novel Anti-cancer Agents in Participants With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy](https://onco.cc/trials/nct03334617/), [Study of AK119 Combined With AK112 in Patients With Advanced Solid Tumors](https://onco.cc/trials/nct05689853/), [Study of Gemcitabine, Cisplatin, AB680 and AB122 During First Line Treatment of Advanced Biliary Tract Cancers (QUIC)](https://onco.cc/trials/nct06048133/), [Study of Inupadenant (EOS100850) With Chemotherapy as Second Line Treatment for Nonsquamous Non-small Cell Lung Cancer](https://onco.cc/trials/nct05403385/), [Study of Novel Treatment Combinations in Patients With Lung Cancer](https://onco.cc/trials/nct05633667/), [Study of Quemliclustat and Chemotherapy Versus Placebo and Chemotherapy in Patients With Metastatic Pancreatic Ductal Adenocarcinoma](https://onco.cc/trials/nct06608927/), [Study With Various Immunotherapy Treatments in Participants With Lung Cancer](https://onco.cc/trials/nct05676931/), [The Selective Personalized Radio-Immunotherapy for Locally Advanced Non-Small Cell Lung Cancer Trial 2](https://onco.cc/trials/nct07146230/), [TT-4 and TT-10 as Single Agents and in Combination in Subjects With Advanced Selected Solid Tumors and Pleural Mesothelioma](https://onco.cc/trials/nct04969315/)
- key papers: [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](https://onco.cc/key-papers/paper-herbst-j-clin-oncol/)
- targets: [Adenosine A2A receptor (ADORA2A)](https://onco.cc/targets/adora2a/), [CD39 (ENTPD1)](https://onco.cc/targets/entpd1/)
- terms: [Checkpoint (two meanings)](https://onco.cc/terms/checkpoint/)

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