Project Details
Projekt
Inflammatory pathways in subtypes of intestinal cancer
Subject Area
Gastroenterology
Biochemistry
Biochemistry
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 515991405
Immune signals derived from cancer cells or the host environment drive intestinal tumour progression and treatment resistance. However, the molecular and cellular mechanisms underlying the local cross-talk between cancer cells and the immune system have not been systematically defined yet. In our previous work, we characterized how different genetic routes and the molecular makeup of the primary tumour reprogram the inflammatory tumour microenvironment (TME) of intestinal cancer subtypes and how immune evasion drives tumour progression in a context specific manner. Moreover, we have developed cell type-specific mass spectrometry (MS)-based proteomics approaches using engineered methionyl-tRNA synthetase (MetRS*) to dissect intercellular cross-talk in tissues and circulation in vivo unbiasedly on the level of proteins. We will now combine our complementary expertise to pursue two major aims: 1) The system-wide characterization of cancer – immune cell cross-talk in tissues and circulation, and 2) The functionalization of tumour–host interactions by systematic genetic interrogations. In aim 1, we will decode tumor/TME communication networks by integrating 1) cell type specific MetRS*proteomics, with (2) transcriptional activity profiling; and 3) multiplexed (phospho)proteomic tissue imaging. These technologies will allow the first unbiased protein-centric and system-wide characterization of cancer – immune cell cross-talk in tissues and circulation in vivo and will be applied to study the paracrine signalling between cancer cells, immune cells and fibroblasts. Thereby, we will create cell communication and neighbourhood maps that integrate the complex molecular makeup of the disease. In aim 2, we will functionalize the cross talk between cancer cells and the TME by genetic loss- and gain-of-function studies in vivo. Thereby, we aim at perturbing immunosuppression and activate a robust anti-tumour immune response.
DFG Programme
Research Grants
