Abstract
Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers in the world. PDAC cells activate tumour-specific immune responses but simultaneously trigger a strong immunosuppression. We showed that PDAC cells produce high amount of chronic inflammatory mediators and PDAC tumours build an immunosuppressive cytokine milieu, which correlates with tumour progression. On the cellular level, we found that tumours from the murine Panc02 orthotopic model of PDAC were infiltrated with high numbers of regulatory T cells (Treg). Remarkably, these cells exhibited the effector/memory phenotype, suggesting their enhanced suppressive activity and higher proliferation capacity. With regard to the innative immune cells, we observed a pronounced accumulation of macrophages and myeloid-derived suppressor cells (MDSC) in murine PDAC tumours. Whilst macrophages seem not to play a significant role in this PDAC model in the context of immunosuppression, MDSC are highly suppressive, and their accumulation is associated with an increase in intratumoural vascular endothelial growth factor (VEGF) concentration during the PDAC progression. Thus, Treg and MDSC are strongly involved in the PDAC-associated immunosuppression and their depletion could provide the base for new approaches for therapy of PDAC.
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