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SP7 Role of pattern recognition receptors and microbiome-derived growth promoting signals in tumor-immune cell interaction in PDAC

Prof. Stefan Bauer

Prof. Malte Buchholz

Prof. Thomas Gress

Pattern recognition receptors (PRRs), which include the toll-like receptors (TLRs), play central roles in the innate immune system. They are highly expressed in tumor-associated macrophages (TAMs), but interestingly also in tumor cells themselves. Focusing on the role of TLR7 in the first funding period, we demonstrated that TLR7 promotes tumor cell growth in vitro, while global TLR7 knockout in KPC and KC mouse models did not alter overall tumor growth, probably due to opposing effects in the epithelial and stromal compartments of the tumor microenvironment. Moreover, we generated preliminary data demonstrating tumor-promoting effects of microbiome-derived factors which may be mediated via PRR stimulation. In the second funding period, we therefore plan to i) analyze the potential of different PRRs to mediate tumor cell growth in response to stimulation with endogenous ligands and/or microbiome-derived factors in vitro; ii) characterize the influence of microbiome-derived factors on the interaction between tumor cells and TAMs in vitro; iii) analyze the role of PRRs in mediating growth-stimulatory effects of gut microbiome-derived signals in gnotobiotic mouse models in vivo; and iv) continue identification and characterization of endogenous PRR ligands that promote PRR-mediated tumor progression.