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SP8 Regulation of NK cells through extracellular vesicles and microbiota released metabolites in PDAC 

Prof. Elke Pogge von Strandmann

The critical role of NK cells in tumor immunosurveillance is widely accepted, but the tumor-dependent suppression of NK cell activity in PDAC and consequently NK cell-based immunotherapies are relatively underexplored. We specifically investigate the biogenesis of extracellular vesicles released by tumor cells and their impact on NK cell functions. Tumor cell-derived EVs inhibit NK cell cytotoxicity and instead promote an exhaustion phenotype in NK cells from healthy donors. Based on this data we will dissect EV-mediated in vivo mechanisms, which reprogram NK cells within the immune suppressive and tumor-promoting PDAC-microenvironment (TME) using a Pan02-transplantation model. The phenotype and the activity of tumor associated NK cells (TANK) will be analyzed in detail and the potential of identified EV-associated factors as biomarkers will be analyzed. Expected results will be validated in human samples. Perpectively, the data obtained will be used to design therapeutic EVs which are able to overcome NK cell-inhibition and instead stimulate NK cell activity to improve NK cell-based immunotherapies for PDAC.