SP10: Dissecting adaptation of the microbiome and the immune environment in biliary tract and pancreatic cancer upon systemic therapies
Recent data suggest that the microbiome exerts profound effects on tumor initiation, progression and therapeutic response. On a molecular level, microbes and microbiome-derived metabolites interact with the intestinal and intratumoral immune compartment. BTC and PDAC are characterized by a distinct inflammatory tumor microenvironment (iTME) that contains a heterogeneous set of immune cells and so far poorly characterized microbes. Importantly, the interplay between entity-specific and overlapping intra-tumoral microbes and immune cells and their dynamic changes upon systemic therapies are poorly understood in BTC and PDAC, but may open new, potentially overlapping treatment avenues. While the group of Albrecht Neesse has established a sophisticated microbiome sequencing platform using 3rd generation 16S rRNA /metagenomics Oxford Nanopore Sequencing in translational mouse models and various human samples, Bernd Heinrich has profound expertise in exploring alterations of the intratumoral immune system using high-dimensional scRNA-seq and protein profiling (multiparameter Flowcytometry, AbSeq/CiteSeq).
The PhD- (Heinrich group) and MD- (Neesse lab) candidates of the first cohort will establish a preclinical BTC and PDAC platform to investigate the inflammatory immune environment along the intestinal and intra-tumoral microbiome upon systemic chemotherapy administration. The PhD- (Neesse lab) and MD- (Heinrich group) candidates of the second cohort will perform functional assays and exploit pharmacological interference strategies to overcome the adaptive state of the chemotherapy induced phenotype to re-sensitize tumors to conventional therapeutics.
Taken together, we aim to better understand microbiome and immune-mediated mechanisms of chemotherapy-induced adaptations to better understand and therapeutically exploit mechanisms of microbiome-mediated adaptive states.
