Fibroblast-regulated immune surveillance in colorectal cancer

There is a large need for improved biomarkers and treatments in colorectal cancer (CRC). Immune surveillance plays a large part in the natural course and treatment sensitivity of CRC.

Previous studies have largely neglected the regulatory roles of fibroblasts in immune regulation and have failed to consider regulatory processes in tumor draining lymph nodes.This project tests the hypothesis that well-informed  profiling of paired primary tumors and tumor draining lymph nodes can identify novel clinically relevant immune-regulatory processes with drug target and biomarker potential.The discovery-focused sub-study 1  use imaging mass cytometry for high-content in situ tissue profiling to identify novel fibroblast-regulated immune niches with preliminary outcome associations.The second sub-studyexpand findings with a multi-marker analysis of selected novel immune features in large clinically well-annotated colorectal cancer collections to explore their biomarker potential.Sub-study 3 use experimental co-culture studies for molecular characterization and CRISPR/Cas9-based target identification in fibroblast-regulated immune pathways suggested by the tissue profiling.Studies are developing large set of preliminary findings.

Feasibility will be ensured by expertise of applicant on tumor microenvironment and tissue profiling, combined with colorectal cancer expertise of partner surgeon, oncologist, pathologist, and support from experts in tumor immunology and CRISPR/Cas9 screens.