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Elke Pogge von Strandmann: The role of HSP70-positive extracellular vesicles from tumor cells for the function of macrophages and NK cells within the ovarian cancer microenvironment

Elke Pogge will investigate to what extent EVs modulate NF-κB signaling in macrophages and NK cells in an HSP70-NF-κB-dependent manner thereby establishing an immune suppressive and tumor-promoting secretome. She will investigate the specific HSP70-TLR/RAGE-dependent NF-κB signaling pathways and their functional consequences in macrophages and NK cells. The association of components within the HSP70-TLR/RAGE-dependent NF-κB-induced secretome with tumor progression and survival of patients will be analyzed to identify potential therapeutic targets.

The role of HSP70-positive EVs on NF-kB-mediated signaling and protein secretion by NK cells and macrophages and consequences for secretome-dependent effects on the TME.
Both project RP2 and RP3 will interact with Lienhard Schmitz (RP4) who has an outstanding track record in the analysis of NF-κB. He will dissect and analyze the NF-κB activity and the NF-κB dependent secretome of ovarian cancer cells and associated immune cells using the 3D organotypic model described in RP2. Experimental tools to analyze the canonical, non-canonical and atypical NF-κB activation pathways at a single cell level are established. In parallel, the impact of pathway-specific NF-κB inhibitors on the secretome of tumor cells and associated immune cells will be measured by mass spectrometry.