Cancers · 2026
Plasma-Derived sEVs from HNSCC Patients Differentially Regulate NF-κB Signaling in Macrophages Depending on the HPV Status.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Huber Diana, Strachwitz Florian von, Hofmann Linda, Pietrowska Monika, Gawin Marta, Chiang Dapi Meng-Lin, Guder Christiane, Lotfi Ramin, Kishida Shosei, Pfaffl Michael W, Wollenberg Barbara, Hoffmann Thomas K, Brunner Cornelia, Theodoraki Marie-Nicole
Аннотация
BACKGROUND: Head 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.
METHODS: sEVs 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.
RESULTS: Proteomic 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.
CONCLUSIONS: Circulating 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.
METHODS: sEVs 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.
RESULTS: Proteomic 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.
CONCLUSIONS: Circulating 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.