# 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/)
- 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/)
- 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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