Hematopoietic aging promotes cancer by fueling IL-1⍺-driven emergency myelopoiesis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39236155.
- Also identified by DOI 10.1126/science.adn0327 and PMC identifier 7616710.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Aging
- DNA Methyltransferase 3A
- Interleukin-1alpha
- Lung Neoplasms
- Macrophages
- Myelopoiesis