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Project A2: Toll-like receptors in tumor progression and as treatment targets in PDAC

Participants:

Prof. Dr. rer. nat. Stefan Bauer
Institute for Immunology
Philipps-Universität Marburg

Prof. Dr. rer. nat. Malte Buchholz
Department of Gastroenterology, Endocrinology, Metabolism and Clinical Infectiology
Philipps-Universität Marburg

Prof. Dr. med. Thomas Gress
Department of Gastroenterology, Endocrinology, Metabolism and Clinical Infectiology
Philipps-Universität Marburg and University Hospital Marburg

Project aims:

Toll like receptors (TLRs) belong to the family of pattern recognition receptors (PRR) which function in the innate immune system to sense pathogen-derived molecules and to initiate an appropriate immune response. Interestingly, TLRs are not only expressed by immune cells but also by cancer cells as well as stroma cells, thus having the potential to influence tumor biology, including therapy resistance, on multiple levels.

In this subproject, we aim to comprehensively characterize tumor cell/microenvironment interactions and the chemoprotective role(s) that TLRs play in this context using in vitro as well as in vivo models of pancreatic cancer. Furthermore, we aim to identify endogenous ligands (e.g. specific tumor-derived chemically modified RNA or DNA fractions) which promote TLR activation. Finally, we will investigate the role of extracellular vesicles (EVs) in tumor cell-macrophage communication and in putative paracrine mechanisms of TLR activation in PDAC tumors.

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