Hematopoietic aging promotes cancer by fueling IL-1⍺–driven emergency myelopoiesis-Reference-Cited by-同舟云学术

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

Published:2024-09-05 Issue: Volume: Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Park Matthew D.¹²³^ORCID,Le Berichel Jessica¹²³^ORCID,Hamon Pauline¹²³^ORCID,Wilk C. Matthias¹²³^ORCID,Belabed Meriem¹²³,Yatim Nader¹²³^ORCID,Saffon Alexis¹²³⁴^ORCID,Boumelha Jesse¹²³^ORCID,Falcomatà Chiara¹²³⁵^ORCID,Tepper Alexander¹²³⁵^ORCID,Hegde Samarth¹²³^ORCID,Mattiuz Raphaël¹²³^ORCID,Soong Brian Y.¹²³^ORCID,LaMarche Nelson M.¹²³,Rentzeperis Frederika¹²³^ORCID,Troncoso Leanna¹²³^ORCID,Halasz Laszlo¹²³^ORCID,Hennequin Clotilde¹²³,Chin Theodore¹²³^ORCID,Chen Earnest P.¹²³^ORCID,Reid Amanda M.¹²³,Su Matthew¹²³^ORCID,Cahn Ashley Reid¹²³,Koekkoek Laura L.¹²⁶,Venturini Nicholas¹²³,Wood-isenberg Shira¹²³,D’souza Darwin¹²⁷^ORCID,Chen Rachel¹²⁷^ORCID,Dawson Travis¹²⁷^ORCID,Nie Kai¹²⁷^ORCID,Chen Zhihong¹²⁷^ORCID,Kim-Schulze Seunghee¹²⁷^ORCID,Casanova-Acebes Maria¹²³^ORCID,Swirski Filip K.¹²⁶⁸^ORCID,Downward Julian⁹¹⁰^ORCID,Vabret Nicolas¹²³,Brown Brian D.¹²³⁵,Marron Thomas U.¹²³¹¹¹²^ORCID,Merad Miriam¹²³⁷^ORCID

Affiliation:

1. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

2. Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

3. The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

4. INSERM U932, Immunity and Cancer, Institut Curie, Paris-Cité University, Paris, France.

5. Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

6. Brain and Body Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

7. Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

8. Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

9. Oncogene Biology Laboratory, Francis Crick Institute, London, UK.

10. Lung Cancer Group, Division of Molecular Pathology, Institute of Cancer Research, London, UK.

11. Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

12. Center for Thoracic Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/science.adn0327

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