Objective: Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide, with secondary hepatic malignancy increasing the CRC mortality rate from 30% to 70%. Currently, there are no prognostic tools to determine the risk of liver metastasis in CRC patients. The presence of tumour infiltrating CD8+ T lymphocytes (Immunoscore) can potentially predict patient survival, however CD8+ T lymphocytes represent a diverse population with distinct functional properties. The aim of this project is to characterise the frequency, phenotype and function of tumour-associated CD8+ T cells in CRC patients and investigate the correlation of specific cell subsets with prognostic clinical endpoints.
Methods: In this study, we collected CRC primary tumours and liver metastases from patients operated at two major South Australian hospitals (Royal Adelaide Hospital and Queen Elizabeth Hospital) and performed flow cytometry to characterise tumour-associated T cells. The prognostic value of identified cell subsets was determined by immunofluorescence using a 200 patient CRC tissue-microarray.
Results: We found evidence for the enrichment of distinct T cell subset with a tissue-residency signature within both primary CRC tumours and liver metastases. Our tissue-microarray analysis suggests that the presence of tissue-resident T cells in primary tumours of TNM stage II patients is associated with shorter progression-free survival and with a higher risk of liver metastasis.
Conclusion: These results suggest a novel immune-tumour interaction promoting metastatic progression in early stage CRC. The presence of tissue-resident T cells will be developed and validated as a prognostic biomarker for the risk of metastatic progression in early stage CRC patients.