Randomized trial demonstrates MDSC accumulation mediated by macrophages in DLBCL, indicating a potential therapeutic target.
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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Liu et al. (2026) studied this question.
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