PhD defence R. (Rachid) Bouzid

Dissertation in short:

My research has focused on various aspects, namely the identification of immune targets through further developing a novel methodology (HLA-immunopeptidomics) that can be applied to discovery in, but not limited to, cancer vaccines. I found that by altering statistical thresholds and implementing an immunological perspective into classic mass spectrometry, the amount of potential targets which can be incorporated and used in vaccine strategies can be increased. Subsequently the antigen presenting cells (namely dendritic cells) can be cultured and fed with synthetic pieces based on proteins of interest in order to induce antigen presentation. The peptides that are eventually presented can be isolated and characterized using our novel HLA-immunopeptidomics pipeline. Furthermore I’ve researched the immune environment of pancreatic cancer patients. In contrary to what was believed earlier due to irresponsiveness to immunotherapy (PD-1 checkpoint inhibitor therapy) in pancreatic cancer, the immune system is heavily involved and attracted to the tumor of these patients. However, I found and confirmed that the effector cells from the immune system (the killer T-cells) are largely excluded from the tumors of patients (partially explaining the irresponsiveness to immunotherapy) and could not find the exact reason for this phenomenon. It was believed that fibroblasts play a major role in this exclusion but unfortunately we were unable to confirm this. However, by confirming the general excluded immune status in these patients, we are able to investigate alternative therapies that target the tumor microenvironment and research their potential to “open up” the tumor and allow for infiltration.