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

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…

• NS
  National Science Foundation
• CR
  Cancer Research Institute
• BS
  Bristol-Myers Squibb
• A
  AstraZeneca
• IS
  Icahn School of Medicine at Mount Sinai
• DK
  Deutsches Krebsforschungszentrum
• RP
  Regeneron Pharmaceuticals
• CT
  Celldex Therapeutics
• AB
  Atara Biotherapeutics
• KI
  Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
• GT
  G1 Therapeutics
• GP
  Glenmark Pharmaceuticals
• SN
  Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
• AP
  Astellas Pharma
• TU
  Technische Universität München
• SC
  Swiss Cancer Research Foundation
• G
  Genentech
• NC
  National Cancer Institute

  Award: K00 CA223043