Macrophage-mediated brain-bone marrow crosstalk promotes chronic stress-induced glioma growth
Menée principalement à l'aide de lignées cellulaires et de modèles murins de gliome, cette étude met en évidence un mécanisme par lequel l'activation du nerf sympathique par le stress chronique favorise la croissance tumorale en induisant la différenciation des monocytes ADRB2+ de la moelle osseuse en macrophages CD45+CD11b+C5aR1+, caractérisés par une accumulation lipidique intracellulaire délétère liée à une expression élevée de l'antigène CD36
Stress is associated with increased cancer morbidity and mortality. Here, we show that chronic stress accelerates glioma growth and reduces survival of tumor-bearing mice. Integrated multi-omics analysis of syngeneic glioma samples reveals stress-induced CD45+CD11b+C5aR1+ macrophages, termed stress-associated macrophages (SAMs). Using parabiosis experiments in mice, we demonstrate that SAMs are derived from bone marrow monocytes. Stress-activated sympathetic nerve promotes the differentiation of ADRB2+ bone marrow monocytes into SAMs, which can be antagonized by selective ablation of catecholaminergic nerves. Conditional knockout of C5ar1 in macrophages, or pharmacologic C5aR inhibition, reduces SAMs and attenuates stress-induced glioma tumor growth in vivo. SAMs exhibit elevated CD36 expression, leading to excessive intracellular lipid accumulation and peroxidization, dampening their phagocytotic capacity. SAMs abundance correlates with self-reported stress levels and portended prognosis in glioma patients. Collectively, these findings suggest that stress reprograms tumor immune microenvironment by inducing molecularly distinguished monocyte-derived macrophages, revealing potential opportunities for immune-based cancer therapies.
Cancer Cell , résumé, 2026