{
  "abstract": "Tumor-associated macrophages (TAMs) possess both tumor-promoting and tumor-inhibiting roles. Here, we explore TAMs' anti-tumor functions, focusing on the immune responsive gene 1 (IRG1) and its product, itaconate, in lung cancer development. Spatial metabolomics reveals that endogenous itaconate is markedly depleted within lung tumor regions compared with adjacent non-tumor tissue. Single-cell RNA sequencing shows that macrophages are the primary cells expressing IRG1 in human and mouse lung tumors. Both IRG1 knockout and transplantation of IRG1-depleted bone marrow leads to increased lung tumor growth in various mouse lung tumor models. Additionally, 4-octyl itaconate (Octyl Ita) reduces tumor growth in vitro, in vivo, and in ex vivo human tumor precision-cut lung slices. An integrated multi-omics analysis shows that IRG1/itaconate causes a metabolic shift in cancer cell and pro-tumor macrophages, mainly by inhibiting the pentose phosphate pathway (PPP) through targeting glucose-6-phosphate dehydrogenase (G6PD) activity, thereby suppressing cancer cell growth and transforming pro-tumor macrophages into anti-tumor macrophages. Thus, leveraging IRG1/itaconate's tumor-suppressive effects or using Octyl Ita could be a novel lung cancer therapy.",
  "abstract_shown": true,
  "affiliations": [
    "Institute for Lung Health (ILH), Justus Liebig University, Giessen, Germany; Max Planck Institute for Heart and Lung Research, German Center for Lung Research (DZL), Cardio-pulmonary Institute (CPI), Bad Nauheim, Germany",
    "The Systems Virology Lab, Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden",
    "Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt, Germany",
    "Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, Free University Medical Center, Amsterdam, the Netherlands",
    "Goethe University Frankfurt, Faculty of Medicine, Institute of Biochemistry I, Frankfurt, Germany",
    "Center for Pathobiochemistry and Genetics, Medical University of Vienna, Vienna, Austria",
    "Department of Core Facilities, Medical University of Vienna, Vienna, Austria",
    "Max Planck Institute for Heart and Lung Research, DZHK German Centre for Cardiovascular Research, Partner Site Rhine-Main, Cardio-Pulmonary Institute (CPI), Bad Nauheim, Germany; Clinical and Translational Glycoscience Research Center, Georgetown University, Washington, DC 20057, USA; Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA",
    "Goethe University Frankfurt, Faculty of Medicine, Institute of Biochemistry I, Frankfurt, Germany; Department for Immunity of Inflammation, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany",
    "Max Planck Institute for Heart and Lung Research, German Center for Lung Research (DZL), Cardio-pulmonary Institute (CPI), Bad Nauheim, Germany",
    "Department of Internal Medicine, DZL, CPI, Justus Liebig University, Giessen, Germany",
    "Department of General and Thoracic Surgery University Hospital Giessen, Giessen, Germany",
    "Department of Pathology, Justus Liebig University, Giessen, Germany",
    "Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria",
    "Institute for Lung Health (ILH), Justus Liebig University, Giessen, Germany; Institute of Molecular Oncology, Philipps-University, Marburg, Germany",
    "Institute for Lung Health (ILH), Justus Liebig University, Giessen, Germany; Department of Internal Medicine, DZL, CPI, Justus Liebig University, Giessen, Germany",
    "Department of Thoracic Oncology, Airway Research Center North, DZL, Lungen Clinic, Grosshansdorf, Germany",
    "Institute for Lung Health (ILH), Justus Liebig University, Giessen, Germany; Max Planck Institute for Heart and Lung Research, German Center for Lung Research (DZL), Cardio-pulmonary Institute (CPI), Bad Nauheim, Germany; Department of Internal Medicine, DZL, CPI, Justus Liebig University, Giessen, Germany"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 27,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Siavash Mansouri",
      "orcid": "0000-0003-0493-5084"
    },
    {
      "affs": [
        0
      ],
      "name": "Golnaz Hesami"
    },
    {
      "affs": [
        1
      ],
      "name": "Anoop Ambikan"
    },
    {
      "affs": [
        0
      ],
      "name": "Annika Karger"
    },
    {
      "affs": [
        2
      ],
      "name": "Stephan Klatt",
      "orcid": "0000-0003-0064-3367"
    },
    {
      "affs": [
        1
      ],
      "name": "Ujjwal Neogi",
      "orcid": "0000-0002-0844-3338"
    },
    {
      "affs": [
        3
      ],
      "name": "Kondababu Kurakula",
      "orcid": "0000-0002-9830-6344"
    },
    {
      "affs": [
        4
      ],
      "name": "Blerina Aliraj",
      "orcid": "0009-0003-1553-7687"
    },
    {
      "affs": [
        5
      ],
      "name": "Anne Miller",
      "orcid": "0000-0002-5587-7497"
    },
    {
      "affs": [
        6
      ],
      "name": "Boryana Petrova",
      "orcid": "0000-0001-9996-9353"
    },
    {
      "affs": [
        7
      ],
      "name": "Miloslav Šanda",
      "orcid": "0000-0002-7735-3635"
    },
    {
      "affs": [
        8
      ],
      "name": "Evelyn Sirait‐Fischer",
      "orcid": "0000-0002-6352-2856"
    },
    {
      "affs": [
        9
      ],
      "name": "Stefan Guenther (5992991)"
    },
    {
      "affs": [
        9
      ],
      "name": "Carsten Tobias Kuenne",
      "orcid": "0000-0001-8013-5906"
    },
    {
      "affs": [
        10
      ],
      "name": "Clemens Ruppert",
      "orcid": "0000-0002-0938-2469"
    },
    {
      "affs": [
        11
      ],
      "name": "Ibrahim Alkoudmani"
    },
    {
      "affs": [
        12
      ],
      "name": "Stefan Gattenlöhner",
      "orcid": "0000-0002-8673-6777"
    },
    {
      "affs": [
        2
      ],
      "name": "Sven Zukunft",
      "orcid": "0000-0002-1811-4562"
    },
    {
      "affs": [
        2
      ],
      "name": "Ingrid Fleming",
      "orcid": "0000-0003-1881-3635"
    },
    {
      "affs": [
        13
      ],
      "name": "Arvand Haschemi",
      "orcid": "0000-0001-9532-3205"
    },
    {
      "affs": [
        14
      ],
      "name": "Thorsten Stiewe",
      "orcid": "0000-0003-0134-7826"
    },
    {
      "affs": [
        15
      ],
      "name": "Friedrich Grimminger",
      "orcid": "0000-0001-8725-6276"
    },
    {
      "affs": [
        16
      ],
      "name": "Martin Reck"
    },
    {
      "affs": [
        8
      ],
      "name": "Andreas Weigert",
      "orcid": "0000-0002-7529-1952"
    },
    {
      "affs": [
        17
      ],
      "name": "Werner Seeger"
    },
    {
      "name": "Soni Savai Pullamsetti",
      "orcid": "0000-0003-0440-8831"
    },
    {
      "name": "Rajkumar Savai",
      "orcid": "0000-0003-1538-2091"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e6y4581842wfe.bib",
  "cited_by": 7,
  "doi": "10.1016/j.cmet.2026.05.005",
  "fulltext_url": null,
  "id": "e6y4581842wfe",
  "issns": [
    "1550-4131",
    "1932-7420"
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  "landing_url": "https://doi.org/10.1016/j.cmet.2026.05.005",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "2403|Immune cells in cancer"
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  "openalex": "W7163423174",
  "pdf_url": null,
  "pmcid": null,
  "pmid": "42235511",
  "published": "2026-06-03",
  "publisher": "Cell Press",
  "ris": "https://research.draconitic.com/paper/e6y4581842wfe.ris",
  "sources": [
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      "first_seen": "2026-10-30T13:26:51Z",
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      "url": "https://doi.org/10.1016/j.cmet.2026.05.005"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune cells in cancer",
      "subfield": "immunology"
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  ],
  "title": "IRG1/itaconate rewires macrophage and lung tumor metabolism through G6PD inhibition",
  "title_text": "IRG1/itaconate rewires macrophage and lung tumor metabolism through G6PD inhibition",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T13:20:33Z",
  "url": "https://research.draconitic.com/paper/e6y4581842wfe",
  "venue": "Cell Metabolism",
  "versions": []
}