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

Dr. Cathriona Foley

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 Residual 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.

Clinical Challenge being addressed: An intraoperative cellular immunotherapy, resilient to postoperative local tissue inflammation and immunosuppression, may clear residual tumour cells following incomplete surgical tumour excision in colorectal cancer patients.

”Colorectal cancer rates are on the rise in young adults. Considering bowel cancer screening begins at 59 years of age in Ireland, more patients may present with later stages of the disease in the years ahead. This research is important as it strives to develop a new protocol for a therapy to treat and prevent metastasis of colorectal cancer” Dr. Cathriona Foley.

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.

References:

Uslu U, Da T, Assenmacher CA, Scholler J, Young RM, Tchou J, June CH. Chimeric antigen receptor T cells as adjuvant therapy for unresectable adenocarcinoma. Sci Adv. 2023 Jan 13;9(2):eade2526. doi: 10.1126/sciadv.ade2526. Epub 2023 Jan 11. PMID: 36630514; PMCID: PMC9833675.

Bruni E, Cimino MM, Donadon M, Carriero R, Terzoli S, Piazza R, Ravens S, Prinz I, Cazzetta V, Marzano P, Kunderfranco P, Peano C, Soldani C, Franceschini B, Colombo FS, Garlanda C, Mantovani A, Torzilli G, Mikulak J, Mavilio D. Intrahepatic CD69⁺Vδ1 T cells re-circulate in the blood of patients with metastatic colorectal cancer and limit tumor progression. J Immunother Cancer. 2022 Jul;10(7):e004579. doi: 10.1136/jitc-2022-004579. PMID: 35863820; PMCID: PMC9310256.

Schematic diagram of the research