Investigation of the Signalling Pathways Underpinning the Enhanced Immunosuppressive Phenotype of Tumour Associated Mesenchymal Stromal Cells (360G-Wellcome-206888_Z_17_Z)

The aim of this project is to understand how stromal cells underlying the colonic crypts interact with the epithelial tumour cells, protecting them from immune mediated destruction. The research objective will be to identify if activation of transcription factors, such as NF-kappa-B and STAT are necessary for the heightened immunosuppressive phenotype observed in tumour conditioned stromal cells. Research will be carried out using syngenic models of colon cancer in vitro, including Balb/c metastatic colon cancer cells, Balb/c mesenchymal stromal cells and Balb/c CD3+T cells. The research, carried out over the course of an 8 week project will aim to; 1. Confirm the potentiated immunosuppressive ability of tumour conditioned stromal cells 2. Investigate if the enhanced immunosuppressive effect is associated with activation of NFkappaB (p65 phosphorylation) and STAT (STAT3 phosphorylation) using western blotting. The desired outcome of this research project, is to understand the signalling pathways that are activated in tumour associated stromal cells that influence their heightened immunosuppressive potential. As part of Dr Ryan's larger research group, ultimately it is envisaged that this research will identify ways in which these interactions can be targeted and blocked, in order to enhance the immune system's effect on the tumour.