TIPTOE - Investigating Peripheral T cell Tolerance in Colorectal Cancer

Interventions: Individuals with stage IV colorectal cancer who are planned to undergo surgery to remove their primary tumour +/- metastatic disease as part of their routine cancer care will be recruited to this study. At the time of surgery, once the specimen has been surgically resected, a number of fresh tissue samples will be obtained from the specimen for the research study. These samples will include lymph nodes, a small sample of the primary tumour, a sample of normal tissue, and a sample of a metastasis. These samples will be obtained by a senior colorectal surgeon under the supervision of pathology staff. In addition, a blood sample (up to 40ml) will be taken from the participant via their routinely inserted peripheral vein cannula once the participant is under general anaesthesia or at the appropriate time prior to surgery co-ordinated with diagnostic sampling by the anaesthetist.
Samples obtained will be processed for single cell RNA sequencing analysis. Remaining tissue, cells and plasma that have been isolated from tissue and blood will be cryopreserved and stored in a secure manner.
Participants will not be required to attend any follow up study visits for this study. The Peter MacCallum Cancer Centre hospital electronic medical record will be reviewed from time of initial diagnosis up to 3 years post-surgery for all participants who choose to enrol. Only relevant clinical data regarding the participant will be obtained and stored in a secure and de-identified manner. This will include basic demographics, diagnosis, stage and site of primary tumour, site(s) of metastatic disease, prior anti-cancer treatment, relapse date, death date and follow up dates, past and concurrent medical history, and concurrent medications at time of surgery.
Primary outcome(s): Identification of a lymph node restricted CD8+ T cell population with a gene expression profile consistent with peripheral tolerance using single cell RNA sequence (scRNAseq) analysis of all obtained samples.[At completion of scRNAseq analysis of all obtained samples]
Study Design: Timing: Prospective