Pancreatic Cancer: Insights from translational and clinical perspectives

This thesis examined various aspects of pancreatic cancer, both through clinical and translational research. The aim of this thesis was to deepen the understanding of the local and systemic tumor microenvironment of pancreatic cancer. In addition, this thesis examined whether resectability of pancreatic cancer can be safely increased by neoadjuvant treatment and more extensive surgery. In Part I, this thesis focuses on the immune system and the microbiome. The immune system plays a crucial role in the development of cancer. It is able to recognize cancer cells at an early stage and eliminate them immediately. If this does not happen successfully, the cancer cells can continue to divide and a tumor develops. Chapter 2 looks at patients who are given drugs to suppress the immune system to prevent rejection of a transplant organ. Next, this thesis focuses further on pancreatic cancer. Chapter 3 examines the immune system in blood of patients with pancreatic cancer, and compares it to patients with non-malignant diseases and healthy people. To examine the regulatory immune responses within the local tumor micro-environment, the research moves from the blood to pancreatic tissue in Chapter 4. Here, the different immune cells in fibrotic pancreatic tissue are compared to normal pancreatic tissue from both patients with pancreatic cancer. In addition to the immune system, there are many other factors that can contribute to the development of cancer, such as age, genetic predisposition and lifestyle. Chapter 5 critically reviews published articles that look at the microbiome of the pancreas. Chapter 6 further focuses on the modulating effects of different patient characteristics on the microbiome of the pancreas. Part II of this thesis focuses on patients with pancreatic cancer where there is (suspected) tumor infiltration into large veins. In these patients, a part of the vein is resected in order to remove the tumor in its entirety. In Chapter 7, the literature examined whether this is safe and useful in the short and long term. Next, Chapter 8 explored whether treatment for patients with suspected venous involvement can be further improved by the addition of neoadjuvant therapy. Finally, Chapter 9 looks at the effect of neoadjuvant therapy on the immune system of patients with pancreatic cancer who underwent venous resection.