The Francis Crick Institute
Browse

Hematopoietic aging promotes cancer by fueling IL-1⍺-driven emergency myelopoiesis.

Download (2.07 MB)
journal contribution
posted on 2024-10-24, 13:52 authored by Matthew D Park, Jessica Le Berichel, Pauline Hamon, C Matthias Wilk, Meriem Belabed, Nader Yatim, Alexis Saffon, Jesse Boumelha, Chiara Falcomatà, Alexander Tepper, Samarth Hegde, Raphaël Mattiuz, Brian Y Soong, Nelson M LaMarche, Frederika Rentzeperis, Leanna Troncoso, Laszlo Halasz, Clotilde Hennequin, Theodore Chin, Earnest P Chen, Amanda M Reid, Matthew Su, Ashley Reid Cahn, Laura L Koekkoek, Nicholas Venturini, Shira Wood-isenberg, Darwin D'souza, Rachel Chen, Travis Dawson, Kai Nie, Zhihong Chen, Seunghee Kim-Schulze, Maria Casanova-Acebes, Filip K Swirski, Julian Downward, Nicolas Vabret, Brian D Brown, Thomas U Marron, Miriam Merad
Age is a major risk factor for cancer, but how aging impacts tumor control remains unclear. Here, 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 IL-1⍺ that drives the enhanced myeloid response. The age-associated decline of DNMT3A enhances IL-1⍺ production, and disrupting IL-1R1 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.

Funding

Crick (Grant ID: CC2097, Grant title: Downward CC2097) European Research Council (Grant ID: 834692 - RASImmune, Grant title: ERC 834692 - RASImmune)

History

Usage metrics

    The Francis Crick Institute

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC