Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, and the second leading cause of cancer-related deaths in Europe. The complexity of its development is attributed to a substantial mutational signature and a complex tumor microenvironment. Present in the tumor microenvironment of CRCs are cancer-associated fibroblasts (CAFs). CAFs play a crucial role in tumor development and progression, and their behavior is regulated by various signaling molecules, including glycosylated proteins. In CRC, CAFs undergo glycosylation changes that can lead to the secretion of immunosuppressive factors such as TGF-β and IL-10, which inhibit the activity of immune cells such as T cells and natural killer cells. Moreover, glycosylated cells in the tumour can induce the differentiation of immune cells into regulatory T cells, further promoting an immunosuppressive microenvironment. Hence we believe that these distinct modifications in glycosylation could serve as a unique characteristic of CAFs, thus offering new opportunities for diagnosis and therapy. This project aims to identify the expression of immunomodulatory proteins in stromal cells extracted from freshly collected prospectively biobanked tissue samples of patients with and without colorectal cancer. The objective of this project would be to first culture stromal cells (both NAFs and CAFs), and normal human MSCs conditioned with tumor cell secretome. Then using flow cytometry and Fc Chimeras, analysis of siglec ligands in the cultured stromal cells are to take place. We hypothesize that the expression of siglec ligands (5,7,9,10) are present in CAFs and that they are pro-tumorigenic.
