ArticleCancers2026
Plasma-Derived sEVs from HNSCC Patients Differentially Regulate NF-κB Signaling in Macrophages Depending on the HPV Status.
Article in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundHead and neck squamous cell carcinomas (HNSCCs) are highly immunosuppressive, and tumor-associated macrophages constitute a major component of HNSCC tumor microenvironments. Here, we investigate the effects of circulating small extracellular vesicles (sEVs) from HNSCC patients on primary macrophages, to elucidate systemic sEV-mediated immune regulation in HNSCC patients.
methodssEVs were isolated from plasma by size-exclusion chromatography. Internalization of PKH26-labeled sEVs was demonstrated, and mass spectrometry analysis was performed on HNSCC sEVs and sEV-treated macrophages. NF-κB activation was investigated by Western blot and p65 translocation assay. Downstream, mRNA and protein levels of cytokines and chemotaxis of T cells were investigated.
resultsProteomic analysis revealed time-dependent modulation of the macrophage proteome and NF-κB signaling pathway, which was confirmed by Western blot and p65 translocation assay. sEVs from HNSCC patients negative for human papillomavirus type 16 (HPV) differentially modulated NF-κB signaling and sEV uptake mechanisms compared with sEVs from HPV-positive patients and healthy donors.
conclusionsCirculating sEVs derived from HNSCC patient plasma modulate macrophage proteomic profiles and NF-κB signaling. HPV16 status was associated with differential sEV-mediated macrophage regulation, suggesting a potential role of sEVs in systemic immune modulation in HNSCC.
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