Journal of extracellular vesicles · 2026
Tumour-Derived Extracellular Vesicles Induce Diffuse Large B-Cell Lymphoma Progression Through Macrophage-Mediated MDSC Accumulation.
СтатьяНазвание и аннотация: Перевод в очереди
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Liu Mengke, Dong YingYu, Guan Qixiao, Wang JianBiao, Shi Qing, Lin RongGui, Zhang Muchen, Fu Di, Cheng Shu, Xu Pengpeng, Angeli Eurydice, Bousquet Guilhem, Cui Wenguo, Dou Hongjing, Zhao Wei-Li, Wang Li
Аннотация
Elevated peripheral myeloid-derived suppressor cells (MDSCs) predicted suppressed anti-tumour immunity and poor prognosis in diffuse large B-cell lymphoma (DLBCL) patients. Here we demonstrated that tumour-derived extracellular vesicles (EVs) served as a messenger, delivering cholesterol from lymphoma cells to macrophages. Through internalisation of tumour-derived EVs, macrophages were activated and secreted IL-1β via the NLRP3/IL-1β axis, leading to IL-1β-mediated MDSC expansion, as well as T cell suppression and exhaustion in DLBCL. Furthermore, macrophage depletion in vitro and in vivo impeded MDSC infiltration induced by tumour-derived EVs. Pharmacological inhibition of cholesterol metabolism with metformin suppressed the secretion of EVs from DLBCL cells, accompanied by decreased IL-1β secretion and MDSC accumulation. Thus, we concluded that tumour-derived EVs induce MDSC accumulation in a macrophage-dependent manner and could be targeted by metformin through inhibition of cholesterol biogenesis in DLBCL.