Specialization
Focus of research
Our principal scientific interest is in cells of the innate immune system and their contribution to the pathogenesis and treatment of disease, specifically related to cancer and immunotherapy. In the past years our group has focused on the role of phagocytes, such as macrophages and neutrophilic granulocytes, during monoclonal antibody therapy in cancer. We have, amongst other things, been exploring the basic mechanisms by which innate immune cells destroy antibody-opsonized cancer cells, which has most recently led us to identify the cytotoxic effector mechanism employed by neutrophils in this context (Matlung et al. (2018) Cell Reports 23:3946). Furthermore, we have been trying to identify the relevant immune checkpoints that control antibody-dependent cellular cytotoxicity (ADCC) by innate immune cells. As such we have found that interactions between CD47 expressed on cancer cells and SIRPα expressed on phagocytes, including neutrophils and macrophages, plays a very important role in limiting ADCC exerted by these cells (Zhao et al. (2011) PNAS 108:18342; Barclay and van den Berg (2014) Annu Rev Immunol. 32:25; Matlung et al. (2017)Immunol Rev. 276:145) . We are currently, in collaboration with Synthon Biopharmaceuticals, developing antagonists of the CD47-SIRPα interaction that we aim to combine with a variety of available cancer antibody therapeutics.
Together with the pediatric immunologists prof. dr. Taco W. Kuijpers our joined research group has also been active in the diagnosis and identification of rare primary immunodeficiency (PID) syndromes As such we have identified a number of novel primary immunodeficiency syndromes in our laboratory, including e.g. Leukocyte adhesion deficiency syndrome type 3 (LAD3) (Kuijpers et al. (2009) Blood. 113:4740) and ARPC1B-deficiency (Kuijpers et al. (2017) J Allergy Clin Immunol. 140:273).
Finally, we have been exploring the interactions of innate immune cells and red blood cells and platelets in other blood cell disorders, specifically in the context of blood transfusion research. As such we have been investigating genetic risk determinants of alloimmunization of transfused Sickle cell disease patients (Meinderts et al (2017) Blood 130:2121).