Investigating the role of the immune landscape in pancreatic ductal adenocarcinoma

Abstract

This project investigates the interplay between host immune response and pancreatic ductal adenocarcinoma. Chapter 1 provides an overview of the incidence, mortality and treatment options for pancreatic cancer in addition to the current molecular understanding of pancreatic cancer. Chapter 2 is a systematic review and meta-analysis of tissue based immune based prognostic biomarkers in pancreatic cancer. We identified high infiltration of CD4 and CD8 T cells associated with improved disease free survival in pancreatic cancer. High CD163 macrophage infiltration was associated with reduced overall survival, suggesting an important role of the immune response in pancreatic cancer outcome. Chapter 3 describes the creation of a Northern Ireland population based cohort of patients who underwent surgical resection of pancreatic cancer since 1996. Clinico-pathological and survival data was retrieved from the Northern Ireland Cancer Registry and multivariable survival analysis of 321 patients undertaken. Corresponding pathology slides were identified from the Belfast Trust histopathology laboratory and Chapter 4 describes how these were processed and uploaded to enable digital pathology analysis. A sample of the cohort was selected and the QuPath program used to undertake analysis of the association between tumour stroma percentage and survival in our cohort. Chapter 5 describes our findings in the context of other work investigating the interplay between immunity and pancreatic cancer survival. It also discusses future research plans now this cohort has been identified and created, including the digital pathology analysis of the entire cohort and construction of tissue microarrays to investigate the association between tumour infiltration by immune cells and survival in our cohort of patients.

Date of Award	Jul 2025
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Royal College of Surgeons & Ulster Society of Gastroenterology
Supervisor	Richard Turkington (Supervisor) & Helen Coleman (Supervisor)