Investigating Minimal Residual Disease Post-Operatively in Patients with Excised Colorectal Cancer Tumours

Dr. Anthonia Ekperuoh, Dr. Cathriona Foley and Amy Walsh

Dr. Anthonia Ekperuoh and Amy Walsh, PhD student joined Dr. Foley’s team through the 5 For The Fight Colorectal Research Fellow in partnership with Breakthrough Cancer Research. In 2023, Dr. Cathriona Foley, in University College Cork was awarded the 5ForTheFight Colorectal Research Fellow in partnership with Breakthrough Cancer Research. The title of her project is “Arming Vδ1 γδ T Cells for Elimination of Minimal Re sidual Disease Post-Operatively in Patients with Excised Colorectal Cancer Tumours.’

Cancer surgery is a life-saving therapy for patients with solid tumours however, for most patients, cancer returns following surgery. This may occur when individual cancer cells remain behind after surgery and hide from protective immune cells in the surrounding tissue. These individual cells multiply and grow into lawless tumours without efficient immune cell policing. Surgical removal of the tumour causes tissue damage in the remaining healthy tissue inducing inflammation. Although some inflammation is good, too much is harmful, and the body reacts by using tools to reduce it. However, these inflammation reducing tools, also make the immune cells incapable of detecting and killing cancer cells left behind after surgery. Providing cancer patients with additional immune cells, resilient to these inflammation reducing tools, would promote better immune cell policing of rogue cancer cells and prevent tumour return following surgery.

This research will develop ways to grow a type of immune cell known as a Vδ1 γδ T cell from blood of any healthy donor, which could be given to any colorectal cancer patient, preventing the return/spread of cancer after surgery. The development of this protocol will benefit from information on individual cells taken from the colorectal cancer primary tumour and metastatic lesions to understand what makes a more resilient Vδ1 cell capable of killing cancer cells in the body.

This research has the potential to develop an enhanced Vδ1 cellular immunotherapy in combination with surgery, for delivery into the tumour excision site to prevent colorectal cancer recurrence and metastasis.

Schematic diagram of the research

RESEARCH FINDINGS

Publications:

Cullinane, C., Connolly, R.M., Corrigan, M., Redmond, H.P. and Foley, C. (2024), Perioperative systemic IL-6 and immune-adipose- metabolism transcription in tumour and tumour adjacent breast cancer. Eur. J. Immunol., 54: 2451049. https://doi.org/10.1002/eji.202451049

Conference Presentations

5th Gamma Delta T Cell Therapies Summit during a workshop session 2024, Boston , USA. Title “Immunotherapy, Surgery and Gamma Delta T cells”. Presenter: Dr. Cathriona Foley.

7th European Congress of Immunology 2024, Dublin, Ireland. Title: “Cytotoxicity of Vδ1 γδ T Cells Isolated from Healthy Donor PBMCs against Colorectal Cancer Cells”. Presenter: Amy Walsh.