ArticleScience (New York, N.Y.)2024
Hematopoietic aging promotes cancer by fueling IL-1⍺-driven emergency myelopoiesis.
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Article in Science (New York, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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99citing papers in PubMed
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Who cites it
99 citing papers in PubMed.
- Immunotherapy and senolytics in head and neck squamous cell carcinoma: phase 2 trial results.Nature medicine · 2025Trial
- IL-1α Expands SLC2A1highSPP1highIFNlow Myeloid Cells to Drive Immune Escape and Malignant Transformation of Precancers.Cancer research · 2026Article
- Age-related IGF-1 decline permits a redox-sensitive transcriptional shift that directs hematopoiesis toward a CCR2Redox biology · 2026Article
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- Pathophysiological roles of monocytes and macrophages in cancer.Nature reviews. Immunology · 2026Review
- Cytotoxic CD4Nature aging · 2026Article
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- Thymulin restrains age-associated myeloid inflammation and enhances cancer immunotherapy.Nature communications · 2026Article
- Age-associated decline of Lamtor5 drives immunosenescence and systemic aging via cGAS-mediated paracrine inflammation.Cell death and differentiation · 2026Article
- Cellular hallmarks and aging clock of the human lung parenchyma.Nature communications · 2026Article
- Article
- Environmental exposures and multiple myeloma risk: A contemporary review of epidemiologic associations and mechanistic plausibility.Blood reviews · 2026Review
- Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers.MedComm · 2026Review
- Article
- The ageing immune system as a driver of systemic ageing.Nature reviews. Immunology · 2026Review
- A Roadmap to Transform Lung Cancer Outcomes: Priorities in Biology, Therapeutic Innovation, Early Detection, Prevention, and Interception.Cancer discovery · 2026Review
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Innovative approaches for lung cancer screening and interception.Nature reviews. Clinical oncology · 2026Review
- Harnessing myeloid cell plasticity for cancer therapy.Nature cancer · 2026Review
- Extracellular vesicles derived from senescent hepatocytes drive pan-cancer metastasis in aging.Nature aging · 2026Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
39 authors.
Matthew D ParkDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0003-3488-3262
Jessica Le Berichel *Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0003-0846-3280
Pauline Hamon *Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-6776-1635
C Matthias Wilk *Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0001-5429-7143
Meriem Belabed *Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Nader YatimDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0001-5326-1624
Alexis SaffonDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0001-7771-4229
Jesse BoumelhaDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0001-7635-2537
Chiara FalcomatàDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0001-9269-2582
Alexander TepperDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0003-1384-9241
Samarth HegdeDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0001-6319-0372
Raphaël MattiuzDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-3292-1635
Brian Y SoongDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0003-4647-7704
Nelson M LaMarcheDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Frederika RentzeperisDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0001-9797-1134
Leanna TroncosoDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0003-2529-9267
Laszlo HalaszDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0003-4726-7012
Clotilde HennequinDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Theodore ChinDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0003-1720-4117
Earnest P ChenDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-1626-5551
Amanda M ReidDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Matthew SuDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0009-0009-9689-5446
Ashley Reid CahnDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Laura L KoekkoekDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Nicholas VenturiniDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Shira Wood-IsenbergDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Darwin D'souzaDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-1943-5173
Rachel ChenDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0009-0004-0021-2561
Travis DawsonDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-9609-793X
Kai NieDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-8253-9688
Zhihong ChenDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0001-7403-7015
Seunghee Kim-SchulzeDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0003-0192-4400
Maria Casanova-AcebesDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-5790-1163
Filip K SwirskiDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-3163-9152
Julian DownwardOncogene Biology Laboratory, Francis Crick Institute, London, UK.ORCID 0000-0002-2331-4729
Nicolas VabretDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Brian D BrownDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Thomas U MarronDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0001-5903-8191
Miriam MeradDepartment of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-4481-7827
Funding
THE TISCH CANCER INSTITUTE - CANCER CENTER SUPPORT GRANTP30CA196521 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Ramon E Parsons · 2015 to 2026
$35.4MHigh-Dimensional Immune Monitoring of NCI-Supported Immunotherapy TrialsU24CA224319 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Sacha Gnjatic, Seunghee Kim-Schulze · 2017 to 2026
$21.5MPET/MRI imaging of mitral valve prolapseR01HL166720 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI David H Adams, Zahi A. Fayad · 2023 to 2026
$8.2MUntargeted Analysis ResourceU2CES030859 · NIEHS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ARORA, MANISH · 2019 to 2025
$8.2MMolecular underpinnings of the developmental Effects of CannabisR01DA055434 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI YASMIN L. HURD · 2022 to 2026
$4.2MSpatial functional genomics to identify regulators of the tumor microenvironment and cancer immunityU01CA282114 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Brian D Brown, MIRIAM MERAD · 2023 to 2026
$4.2MInvestigating Macrophage Molecular and Functional Diversity in Tumor ImmunityR01CA254104 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BROWN, BRIAN D, MERAD, MIRIAM · 2021 to 2025
$3.4MDissecting the pathways driving progenitor to pro-tumor macrophage programmingR01CA257195 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Brian D Brown, MIRIAM MERAD · 2021 to 2026
$3.3MType 2 immunity: a primitive response to epithelial injury that shapes bone marrow and lung myeloid crosstalkR01CA277479 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI MIRIAM MERAD, Thomas Urban Marron · 2023 to 2026
$2.6MDIDACTIC: Dissemination and Implementation of a Diet and Activity Community TrialR01HL122285 · NHLBI · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI BRANDT, HEATHER M, HEBERT, JAMES R · 2014 to 2017
$2.1MDefining the barriers to immune surveillance in solid tumorsK00CA223043 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HEGDE, SAMARTH · 2020 to 2023
$374kNCI NIH HHS K00 CA223043NCI NIH HHS P30 CA196521NCI NIH HHS R01 CA254104NCI NIH HHS R01 CA257195NCI NIH HHS R01 CA277479NCI NIH HHS U01 CA282114NCI NIH HHS U24 CA224319NHLBI NIH HHS R01 HL122285NHLBI NIH HHS R01 HL166720NIDA NIH HHS R01 DA055434NIEHS NIH HHS U2C ES030859Wellcome Trust CC2097
Abstract
Age is a major risk factor for cancer, but how aging impacts tumor control remains unclear. In this study, we establish that aging of the immune system, regardless of the age of the stroma and tumor, drives lung cancer progression. Hematopoietic aging enhances emergency myelopoiesis, resulting in the local accumulation of myeloid progenitor-like cells in lung tumors. These cells are a major source of interleukin (IL)-1⍺, which drives the enhanced myeloid response. The age-associated decline of DNA methyltransferase 3A enhances IL-1⍺ production, and disrupting IL-1 receptor 1 signaling early during tumor development normalized myelopoiesis and slowed the growth of lung, colonic, and pancreatic tumors. In human tumors, we identified an enrichment for IL-1⍺-expressing monocyte-derived macrophages linked to age, poorer survival, and recurrence, unraveling how aging promotes cancer and offering actionable therapeutic strategies.
Indexed as
AgingDNA Methyltransferase 3AInterleukin-1alphaLung NeoplasmsMacrophagesMyelopoiesisAnimalsHematopoiesisHumansInterleukin-1betaMiceMice, Inbred C57BLPancreatic NeoplasmsSignal TransductionDNA Methyltransferase 3AInterleukin-1alphaInterleukin-1beta
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