© Sofía Frigerio
Chronic colonic inflammation in patients with Inflammatory Bowel Disease increases the risk of colitis-associated cancer (CAC). Although mouse studies have been instrumental in understanding CAC development, the immune cell composition and the role of these immune cells in human CAC are largely unknown.
In this study, we aim to decipher the composition and characteristics of immune cells in close proximity to dysplastic pre-cancerous lesions and cancers in IBD patients, and to decipher possible interactions between epithelial cells and the underlying immune cell populations in these regions, using novel spatial profiling techniques.
We will collect formalin-fixed paraffin-embedded (FFPE) tissues from sporadic or CAC dysplastic lesions and carcinomas from our existing biobanks. These FFPE tissues will be processed to make tissue microarrays allowing the study of up to 50 regions on a single slide. These slides will be analysed using imaging mass cytometry and digital spatial profiling, which will allow us to identify (1) the immune cell composition in high detail and (2) the transcriptome in immune and epithelial cells in these specific regions of interest, all without losing spatial context.
To improve preventive strategies and identification of patients at risk, it is critical to understand the aetiology of CAC. Attempts to identify differences in mutations between sporadic colorectal cancer and CAC have been unsatisfactory, and while pro-inflammatory mediators have been identified to play a role in driving colorectal cancer in mice, their contribution to human CAC is unknown. Moreover, it has become clear in the era of immunotherapy for cancer that immune cells play a critical role in clearance of pre-cancerous cells. We believe that this research will further extend our knowledge on the role of the immune system in CAC and will provide future avenues to improve CAC diagnostic and treatment.
The proposed project will last one year, starting in October 2022 and ending in October 2023.