Investigating the role of tumour-associated immune cell subsets in human colorectal cancer liver metastasis (#214)
Colorectal cancer (CRC) is the third most common cause of cancer-related death worldwide. While the survival rate of early stage primary CRC patients is high, the 5-year survival rate of metastatic CRC (mCRC) patients drops to about 11%. The liver is the primary site of haematogenous metastasis for CRC, and yet currently the only treatment option for mCRC patients is liver resection with a 1-year survival rate of 36%. Immunotherapy is a promising treatment option for mCRC, however the liver presents unique challenges such as having distinct immune cell populations and a tolerogenic microenvironment. The aim of this project is to characterise the phenotype and function of tumour-associated immune cells, with a focus on specific subsets that are enriched in the human liver such as mucosal-associated invariant T (MAIT) cells, and tissue resident CD8+ T cells. Using flow cytometric analysis of liver samples collected from mCRC patients undergoing liver resection, we investigated the frequency and phenotype of immune cell subsets in distal-, proximal-, and metastatic-tissue. Notably, we found evidence for enrichment of distinct subsets with a tissue-residency signature within secondary hepatic tumours. Furthermore, our ongoing ex vivo investigation aims to determine the functional properties of these cell subsets and their potential role in the promotion or elimination of metastatic invasion and tumour survival. The overall goal of this study is to promote the development of prognostic markers and preventative therapies for mCRC.