Focal Adhesion Kinase promotes immune evasion in pancreatic cancer
A study led by our scientists indicates that a protein Focal Adhesion Kinase can promote immune evasion of pancreatic cancer through suppression of antigen processing and presentation.
Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent neoplastic disease of the pancreas (over 9000 new cases every year in the UK alone) accounting for more than 90% of all pancreatic malignancies. It is a highly devastating disease with poor prognosis and rising incidence (linked to obesity, type 2 diabetes and life style habits, including alcohol and tobacco abuse). The 5-year overall survival rate for people affected by PDAC is less than 8%.
PDAC is often difficult to treat. Treatments may include surgery, radiation and chemotherapy. Sadly, they are frequently ineffective and there is an urgent need for better therapeutics that are more likely to prevent eventual relapse. Some researchers and clinicians place significant hope in development of immunotherapies for pancreatic cancer. Immunotherapies are a class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There are already some immunotherapy options for a small subset of patients with pancreatic cancer, and many more are being investigated in clinical trials. Unfortunately, treatment of PDAC with immunotherapies showed limited efficiency so far and there is room for improvement. Consequently, studies that could provide new insights and potential improvements to PDAC immunotherapy are very timely and important.
Recently, Edinburgh Cancer Research investigators from the Institute of Genetics and Cancer led a study which demonstrated that Focal Adhesion Kinase (FAK) - a protein belonging to the family of so called non-receptor tyrosine kinases – regulates antigen processing and presentation in a process that is independent of its kinase activity but requires translocation to the cell nucleus. They discovered that loss of FAK expression in pancreatic cancer cells turned on the expression of other proteins that are required to increase the antigenicity of pancreatic cancer cells, promoting the infiltration of tumour-reactive immune cells known as CD8 T-lymphocytes. The project employed mouse models of pancreatic cancer, analysis of human patient-derived PDAC cell lines and analysis of publicly available human PDAC datasets to conclude that FAK targeted therapies aimed at protein degradation rather than simply kinase inhibition may offer additional therapeutic benefit for the treatment of PDAC.
The project was driven by Dr Marta Canel and supervised by Dr Alan Serrels. It has been published by the journal Gut in the article titled “FAK suppresses antigen processing and presentation to promote immune evasion in pancreatic cancer”. It was supported by funding from Cancer Research UK and Wellcome Trust.
Our work provides novel mechanistic insights into the functions of Focal Adhesion Kinase and other proteins in regulating the immune system in the context of pancreatic cancer. It suggests that therapies aimed at FAK degradation may unlock additional therapeutic benefit for the treatment of PDAC through increasing antigen diversity and promoting antigen presentation.
Related Links
Article in Gut: https://gut.bmj.com/content/early/2023/03/28/gutjnl-2022-327927.long
Dr Alan Serrels Group website: https://www.ed.ac.uk/cancer-centre/research/a-serrels-group
Information about pancreatic cancer: https://www.cancerresearchuk.org/about-cancer/pancreatic-cancer
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