Our joined research group focusses on clinically relevant research questions related to human phagocytes, particularly neutrophilic granulocytes and macrophages. One of our primary interests is to understand, at the cellular and molecular level, the functioning of human neutrophils in the host defense against infection, but also in other diseases, in particular cancer. In this context, we investigate, amongst other things, neutrophils from patients with primary immunodeficiencies, thereby not only providing insights into the genetic and cellular basis of the disease of these patients, but also acquiring fundamental knowledge about the functioning of the human immune system.
Furthermore, we are interested in the cellular effector functions of immunoglobulins in relation to disease. Our research in this area is particularly focused on the properties and therapeutic mechanism(s)-of-action of human immunoglobulin preparations (IVIg) and their effects on Fc-receptor expressing immune cells, such as phagocytes and NK cells. As such, we have a particular interest in the genetics of the human Fc-receptor family in relation to disease, including antibody-mediated autoimmune disease (e.g. AIHA, ITP), alloimmunisation (e.g. Sickle cell disease), Kawasaki disease, and cancer.
We also have an active research line concerning monoclonal antibody therapy in cancer. Here, we investigate, for the purpose of improving the clinical efficacy of monoclonal antibody therapy in cancer the therapeutic targeting of the innate immune checkpoint formed between the ‘don’t-kill-me’ signal CD47 and the myeloid inhibitory receptor SIRP. We are also investigating the cytotoxic mechanisms by which neutrophils killing antibody-opsonized cancer cells. Finally, we are investigating the role of so called myeloid-derived suppressor cells that are found in cancers and the blood of cancer patients, and that have been found to suppress T cell-mediated anti-cancer immunity.
Clinical studies at Sanquin