ArticleNature communications2023
Metabolic Reprogramming via ACOD1 depletion enhances function of human induced pluripotent stem cell-derived CAR-macrophages in solid tumors.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 108 citations in OpenAlex.
- Robust structural, kinetic and biophysical characterization of wild-type human ACOD1, selected mutants and their interaction with citraconate.Journal of structural biology: X · 2026Article
- Next-generation macrophage engineering in cancer therapy: From TAM reprogramming to CAR-macrophages.Molecular therapy. Nucleic acids · 2026Review
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Pathophysiological roles of monocytes and macrophages in cancer.Nature reviews. Immunology · 2026Review
- Chimeric antigen receptor-macrophages: A new paradigm for cell therapy.Bioengineering & translational medicine · 2026Review
- Harnessing macrophage signaling pathways and scalable engineering for next-generation immunotherapies.Signal transduction and targeted therapy · 2026Review
- Induced pluripotent stem cell-derived macrophages (iMacs) in translational medicine: Disease models, drug testing, and therapeutic applications.Molecular biology reports · 2026Review
- CD47 monoclonal antibody enhances the inhibitory effect of anti-HER2 chimeric antigen receptor macrophages on ovarian cancer.Oncology letters · 2026Article
- The oocyte-enriched metabolite serotonin alleviates cellular senescence and aging phenotypes in the mouse.The EMBO journal · 2026Article
- Review
- Metabolic modulation of immune cell function: mechanisms and therapeutic implications in cancer immunotherapy.Oncogenesis · 2026Review
- Optimizing next-generation CAR-macrophages against solid tumors: challenges and potential strategies.Journal of hematology & oncology · 2026Review
- Systematic Proteomic Characterization of EV-A71-Infected Mice Identifies Dynamic Molecular Changes and Therapeutic Targets.MedComm · 2026Article
- Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.Precision clinical medicine · 2026Review
- ACOD1 expression in patients with sepsis: an exploratory study of associations with disease severity and immune signatures.BMC infectious diseases · 2026Article
- Viscoelastic hydrogel primed CAR-macrophage for pulmonary fibrosis treatment.Nature communications · 2026Article
- CAR-macrophages: a new chapter in cancer immunotherapy.Acta biochimica et biophysica Sinica · 2026Article
- Tumor-Associated Macrophages as Therapeutic Targets: Deciphering Interaction Networks and Advancing Clinical Translation.MedComm · 2026Review
- Mitochondrial pyruvate metabolism in club cells drives airway inflammation.Stem cell reports · 2026Article
- Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pro-inflammatory state of macrophages, underpinned by their metabolic condition, is essentially affecting their capacity of combating tumor cells. Here we find, via a pooled metabolic gene knockout CRISPR screen that KEAP1 and ACOD1 are strong regulators of the pro-inflammatory state in macrophages. We show that ACOD1 knockout macrophages, generated in our induced pluripotent stem cell-derived CAR-macrophage (CAR-iMAC) platform, are strongly and persistently polarized toward the pro-inflammatory state, which manifests in increased reactive oxygen species (ROS) production, more potent phagocytosis and enhanced cytotoxic functions against cancer cells in vitro. In ovarian or pancreatic cancer mouse models, ACOD1-depleted CAR-iMACs exhibit enhanced capacity in repressing tumors, leading to increased survival. In addition, combining ACOD1-depleted CAR-iMACs with immune checkpoint inhibitors (ICI), such as anti-CD47 or anti-PD1 antibodies, result in even stronger tumor suppressing effect. Mechanistically, the depletion of ACOD1 reduces levels of the immuno-metabolite itaconate, allowing KEAP1 to prevent NRF2 from entering the nucleus to activate an anti-inflammatory program. This study thus lays down the proof of principle for targeting ACOD1 in myeloid cells for cancer immunotherapy and introduces metabolically engineered human iPSC-derived CAR-iMACs cells with enhanced polarization and anti-tumor functions in adoptive cell transfer therapies.
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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.