ArticleeLife2023
The CD73 immune checkpoint promotes tumor cell metabolic fitness.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Reprogramming of TLR-Ferroptosis Signaling and Immunometabolic Pathways Overcomes Myeloid Suppression to Improve Checkpoint Blockade in Prostate Cancer.Cancer research · 2026Article
- A Targetable Developmental Program Coregulates Angiogenesis and Immune Evasion in Melanoma.Cancer discovery · 2026Article
- CD73 blockade enhances antitumor efficacy of oHSV in solid tumors by increasing macrophage-mediated antigen presentation.Journal for immunotherapy of cancer · 2026Article
- Adenosine signaling in tumor immune escape: metabolic checkpoints, myeloid suppression, and combination immunotherapy.Frontiers in oncology · 2026Review
- Research progress of CD73-adenosine signaling regulating hepatocellular carcinoma through tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2025Review
- The progress and prospects of targeting the adenosine pathway in cancer immunotherapy.Biomarker research · 2025Review
- Development of CD73 Inhibitors in Tumor Immunotherapy and Opportunities in Imaging and Combination Therapy.Journal of medicinal chemistry · 2025Review
- Mechanistic optimization of inavolisib combined with CDK4/6 inhibitors in the treatment of PIK3CA-mutated breast tumors.Frontiers in immunology · 2025Review
- Regulation of CD73 on NAD metabolism: Unravelling the interplay between tumour immunity and tumour metabolism.Cell communication and signaling : CCS · 2024Review
- CD73/adenosine dynamics in treatment-induced pneumonitis: balancing efficacy with risks of adverse events in combined radio-immunotherapies.Frontiers in cell and developmental biology · 2024Review
- The interplay between the DNA damage response and ectonucleotidases modulates tumor response to therapy.Science immunology · 2023Review
- Tumor intrinsic and extrinsic functions of CD73 and the adenosine pathway in lung cancer.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD73 is an ectonucleotidase overexpressed on tumor cells that suppresses anti-tumor immunity. Accordingly, several CD73 inhibitors are currently being evaluated in the clinic, including in large randomized clinical trials. Yet, the tumor cell-intrinsic impact of CD73 remain largely uncharacterized. Using metabolomics, we discovered that CD73 significantly enhances tumor cell mitochondrial respiration and aspartate biosynthesis. Importantly, rescuing aspartate biosynthesis was sufficient to restore proliferation of CD73-deficient tumors in immune deficient mice. Seahorse analysis of a large panel of mouse and human tumor cells demonstrated that CD73 enhanced oxidative phosphorylation (OXPHOS) and glycolytic reserve. Targeting CD73 decreased tumor cell metabolic fitness, increased genomic instability and suppressed poly ADP ribose polymerase (PARP) activity. Our study thus uncovered an important immune-independent function for CD73 in promoting tumor cell metabolism, and provides the rationale for previously unforeseen combination therapies incorporating CD73 inhibition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.