Tumour-Derived Extracellular Vesicles Induce Diffuse Large B-Cell Lymphoma Progression Through Macrophage-Mediated MDSC Accumulation
Mengke Liu, YingYu Dong, Qixiao Guan, JianBiao Wang, Qing Shi, RongGui Lin, Muchen Zhang, Di Fu, Shu Cheng, Pengpeng Xu, Eurydice Angeli, Guilhem Bousquet, Wenguo Cui, Hongjing Dou, Wei-Li Zhao, Li Wang
Journal：Journal of Extracellular Vesicles
IF：21.7
DOI：10.1002/jev2.70309
PMID：
Published：2026-06-10
research field：肿瘤学分子生物学细胞生物学免疫学血液学
Abstract
ABSTRACT 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.
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