Modulatorische Effekte von HNSCC-abgeleiteten Exosomen auf die mitochondriale Atmungsfunktion von PBMCs

Introduction:Mitochondria, commonly known as cellular energy centers, play critical roles in maintaining redox balance and regulating cell death. Research shows that mitochondria can be influenced by extracellular vesicles, such as exosomes, released by cancer cells into the bloodstream. Exploring this impact supports the development of novel therapies.

Methods:Peripheral blood mononuclear cells were isolated from healthy donor blood using density gradient centrifugation, and tumor-derived exosomes (TEXs) were obtained from HNSCC cell line (SAS) and patient plasma using size-exclusion chromatography kit (Exo-spine). Exosome isolation was confirmed by particle size measurement and tetraspanin/Hsp70 expression analysis using ZetaView and flow cytometry, respectively. Stimulated PBMCs were co-cultured with TEX from various sources, and mitochondrial oxygen consumption rates were measured via high-resolution respirometry (Oroboros).

Results:The results revealed significantly decreased mitochondrial oxygen consumption in stimulated PBMCs upon incubation with cell lines-derived TEXs. In contrast, PBMCs treated with patient-derived TEXs showed a less pronounced response. However, among patients with HNSCC, two distinct response patterns were observed; one group exhibited a substantial decline in oxygen consumption, while the other showed minimal to no change.

Conclusion:TEXs can reduce PBMC mitochondrial respiration, though the impact varies based on their sources. Greater heterogeneity in response to the patient-derived TEX may be influenced by individual patient factors. These findings emphasize the complexity of TEXs" impacts on immunity and highlight the need for further research to elucidate the underlying mechanisms for therapeutic applications

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