The aim of this thesis is to unite the fields of immunology, surgery and oncology centring on the study of the dendritic cell, a tall order by any standards. And to have a fighting chance of realizing this objective in a PhD programme, one is forced to pick and focus on one or two facets of each area, in the sanguine anticipation that the in depth study of a particular topic will lead to the discovery of enduring scientific principles that have broad applications in medical science.
Chapter 1 of the thesis begins with a literature review to introduce the blood dendritic cell (DC) (the protagonist of this work), its central role in the immune system, and significance in surgical stress and cancer. The effect of surgery and cancer on the body's immune system has been known for a long time, but how they impact on the DC (as initiator of immune response) per se remains to be clarified.
Chapter 2 of this thesis investigates this question by employing a new rare cell enumeration technology in patients undergoing surgery in an everyday clinical situation. This study broadened to look at physical stress in healthy individuals and more major surgical stress in patients. Not only has DC research been hampered by the scarcity and difficulty in isolating these cells, their dismal in vitro viability has limited their investigation and clinical application.
Next, Chapter 3 explores a novel cell culture system that seeks to afford greater DC viability and survival in vitro. The establishment of this culture system facilitated the original investigation into DC propagation, differentiation/maturation and antigen uptake, but more importantly, provides an essential as well as practical platform for the development of immunotherapy protocols using blood DCs.
Chapter 4 details this project that enrolled over 80 patients over a period of 3 years to evaluate the effects of early and advanced breast cancer on blood DCs. Changes in DC counts were followed up for a period of 12 months.
Chapter 5 concludes this thesis and discusses the importance and relevance of DC monitoring in clinical practice especially in cancer patients, the significance of the baseline results obtained from studying breast cancer patients and the potential exploitation of the new culture system in the development of DC vaccines.