Colorectal cancer (CRC) is the third most common cancer type and the second leading cause of cancer-related deaths in the world. Approximately one in four patients present with distant metastases at primary diagnosis, a condition associated with a very poor prognosis—i.e. a five-year survival rate of 11%. The second most common region for metastases to occur is the membrane lining the abdomen, termed the peritoneum. To date, peritoneal metastases (PM) are being treated by cytoreductive surgery (CRS) followed by a hyperthermic intraperitoneal chemotherapy (HIPEC) treatment. This treatment, however, is suboptimal since approximately 75% of these patients will relapse within 3 years. This high recurrence rate can in part be explained by the immunosuppressive status of the peritoneum after surgery which enhances the immune escape of residual cancer cells.
During my PhD we will try to find a new treatment for colorectal PM, based on locoregional (intraperitoneal) immune modulation, in which we want to engineer the tumor microenvironment (TME) in such a way that the immunosuppressive peritoneum can be converted in a more immunostimulatory environment. Based on recent evidences in the literature, we will focus on intraperitoneal administration of toll-like receptor (TLR) agonists. To study our hypothesis efficiently, we will establish a syngeneic CRC PM mouse model, as well as a clinically relevant tumoroid model. We thus hope that locoregional stimulation of specific TLRs, either alone or in synergy with immune checkpoint inhibitors, might be an effective treatment for colorectal peritoneal carcinomatosis.