美国西奈山伊坎医学院
研究人员确定了免疫系统的衰老，无论基质和肿瘤的年龄如何，都会推动肺癌的进展。造血系统老化增强了紧急髓系造血，导致髓系祖细胞样细胞在肺部肿瘤中的局部积累。这些细胞是推动增强的髓系反应的主要IL-1?来源。
与年龄相关的DNMT3A下降增强了IL-1?的产生，在肿瘤发展初期破坏IL-1R1信号传导可以使髓系造血恢复正常，并减缓肺、结肠和胰腺肿瘤的生长。在人类肿瘤中，研究人员发现与年龄、较差的生存率和复发相关的IL-1?表达的单核细胞来源巨噬细胞的富集现象，这揭示了衰老如何促进癌症，并提供了可操作的治疗策略。
据了解，年龄是癌症的主要风险因素，但衰老如何影响肿瘤控制尚不清楚。
附：英文原文
Title: Hematopoietic aging promotes cancer by fueling IL-1–driven emergency myelopoiesis
Author: 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, Raphal 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
Issue&Volume: 2024-09-06
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.
DOI: adn0327
Source: https://www.science.org/doi/10.1126/science.adn0327