Nicolas Mytzka

• This thesis focuses on approach of using extracellular vesicles (EVs) excreted by cancer cells for liquid biopsy for companion diagnostic of cancer immunotherapeutics. EVs are small membrane vesicles derived from cells. The vesicles can contain most types of biological molecules from the parent cell. By transferring signaling molecules between cells, EVs have an important role in intercellular communication such as immune regulation. This makes them to an interesting target for immunotherapy. The programmed death-ligand 1 (PD-L1) is an immune checkpoint inhibitor which suppresses the immune response. Because of this, it was chosen as target for the analysis of the vesicular content of EVs. To use EVs as a diagnostic tool for liquid biopsy, it is necessary to differ between EVs excreted from healthy cells and EVs excreted from cancer cells. Due to the Warburg effect, cancer cells have a different intracellular pH than healthy cells. If this effect is also present in EVs, the vesicular pH could be used to separate EVs originating from cancer cells.