Introduction: Small extracellular vesicles (sEVs) are released by all cells to enable intercellular communication. Tumor-derived EVs (TEX), often found in cancer patients' plasma and saliva, are known to weaken anti-tumor immune responses through proteins like PDL-1 and CD44v3 and RNAs like miRNA. Research also suggests TEX may alter metabolism, though their precise effects on the tumor microenvironment remain unclear. This study investigates how TEX influence protein, carbohydrate, and lipid metabolism in recipient cells.

Methods: sEVs were isolated from the plasma of head and neck squamous cell carcinoma (HNSCC) patients by size exclusion chromatography.To investigate the interaction between sEV and protein, carbohydrate, and lipid metabolism, different cell types (e.g. UD-SCC-5, HUVEC) were treated with TEX over different time periods. Label-free mid-infrared optoacoustic microscopy (MiROM) and multiphoton microscopy were used to detect changes in metabolism. Additionally, metabolic changes were validated by immune assays and -omics analyses.

Results: Label-free metabolic imaging indicates early changes in lipid metabolism, but not in metabolism related to proteins and carbohydrates, after treatment of UD-SSC-5 with TEX. For HUVEC cells no significant differences in the metabolism after co-incubation with TEX of HNSCC patients were detected. Further immune assays and -omics results support these observations. Changes in proteins were visible at later time points.

Summary/Conclusion: The results of this study support the hypothesis of the connection between TEX and changes in metabolism. While the metabolites of nonmalignant HUVEC cells remained unaltered after treatment with TEX of HNSCC patients, the lipid metabolism of HNSCC cells was altered.

Nein