Marjolein van Egmond More on research
Inflammation and cancer
A primary role of phagocytic cells (e.g. neutrophils and macrophages) is phagocytosis. As such, they express a variety of receptors that recognize pathogens directly, as well as receptors that recognize complement factors (complement receptors) or antibodies (Fc receptors), which facilitates phagocytosis. In addition, neutrophils and macrophages can secrete many difference chemokines and cytokines that will influence other (immune) cells. Macrophages are also involved in wound healing, since they can produce a plethora of growth and angiogenic factors.
The research in our research group is clustered in two related topics: 1. Monoclonal antibody therapy of cancer (theme Cancer Immunology) 2. The role of neutrophil IgA Fc receptor (Fc RI) in health and disease (theme Mucosal Immunology).
1. Monoclonal antibody therapy of cancer (theme Cancer Immunology)
Because both neutrophils and macrophages and have potent cytotoxic abilities we are examining whether it is possible to enlist this potential for tumour cell killing. Both myeloid cell types express Fc receptors and are, as such, able to recognize and kill tumour cells in the presence of specific monoclonal antibodies (mAbs) that opsonize tumour cells. Neutrophils induce tumour cell death especially in the presence of monoclonal antibodies of the IgA subclass. Moreover, we have demonstrated that macrophages are extremely efficient in phagocytosing and digesting cancer cells in the presence of specific IgG mAbs. Our pre-clinical finding that pre-operative IgG mAb therapy prevents development of liver metastases after surgery for colorectal cancer has resulted in the design of a clinical trial that started in November 2016. We are currently investigating the mechanisms of neutrophil- and macrophage mediated tumour cell killing in more detail, as we anticipate that this knowledge will help us to develop novel (pre-operative) adjuvant anti-cancer therapies.
2. The role of neutrophil IgA Fc receptor (Fc RI) in health and disease (theme Mucosal Immunology)
IgA is the principal antibody in mucosal areas and plays a key role in mucosal defence. Neutrophils become highly activated when their IgA Fc receptor (Fc RI) is targeted. Since neutrophils are the first cells to arrive at inflammatory (mucosal) sites upon invasion by pathogens, we postulate that activation of neutrophil Fc RI by IgA-coated microorganisms will trigger an essential immune response that will help to clear the infection. However, aberrant IgA deposits are found in several diseases (e.g. IgA-induced blistering diseases and rheumatoid arthritis). We showed that a perpetuating inflammatory loop is initiated when excessive IgA complexes are present, which leads to sever tissue damage. We therefore aim to unravel the role of IgA- induced neutrophil activation in protective and harmful immune responses in more detail.