TY - JOUR
T1 - Hematopoietic aging promotes cancer by fueling IL-1a–driven emergency myelopoiesis
AU - Park, Matthew D.
AU - Le Berichel, Jessica
AU - Hamon, Pauline
AU - Wilk, C. Matthias
AU - Belabed, Meriem
AU - Yatim, Nader
AU - Saffon, Alexis
AU - Boumelha, Jesse
AU - Falcomatà, Chiara
AU - Tepper, Alexander
AU - Hegde, Samarth
AU - Mattiuz, Raphaël
AU - Soong, Brian Y.
AU - LaMarche, Nelson M.
AU - Rentzeperis, Frederika
AU - Troncoso, Leanna
AU - Halasz, Laszlo
AU - Hennequin, Clotilde
AU - Chin, Theodore
AU - Chen, Earnest P.
AU - Reid, Amanda M.
AU - Su, Matthew
AU - Cahn, Ashley Reid
AU - Koekkoek, Laura L.
AU - Venturini, Nicholas
AU - Wood-Isenberg, Shira
AU - D’souza, Darwin
AU - Chen, Rachel
AU - Dawson, Travis
AU - Nie, Kai
AU - Chen, Zhihong
AU - Kim-Schulze, Seunghee
AU - Casanova-Acebes, Maria
AU - Swirski, Filip K.
AU - Downward, Julian
AU - Vabret, Nicolas
AU - Brown, Brian D.
AU - Marron, Thomas U.
AU - Merad, Miriam
N1 - Publisher Copyright:
© 2024 the authors,
PY - 2024/10/25
Y1 - 2024/10/25
N2 - 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)–1a, which drives the enhanced myeloid response. The age-associated decline of DNA methyltransferase 3A enhances IL-1a 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-1a–expressing monocyte-derived macrophages linked to age, poorer survival, and recurrence, unraveling how aging promotes cancer and offering actionable therapeutic strategies.
AB - 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)–1a, which drives the enhanced myeloid response. The age-associated decline of DNA methyltransferase 3A enhances IL-1a 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-1a–expressing monocyte-derived macrophages linked to age, poorer survival, and recurrence, unraveling how aging promotes cancer and offering actionable therapeutic strategies.
UR - http://www.scopus.com/inward/record.url?scp=85207334958&partnerID=8YFLogxK
U2 - 10.1126/science.adn0327
DO - 10.1126/science.adn0327
M3 - Article
C2 - 39236155
AN - SCOPUS:85207334958
SN - 2096-5672
VL - 386
JO - Journal of Bio-X Research
JF - Journal of Bio-X Research
IS - 6720
M1 - eadn0327
ER -