Linde Meyaard Group
Infection & immunity
Blockade of immunological checkpoints is a novel therapeutic approach in cancer. Our group studies the biology of immunological checkpoints. Our basic research line focuses on identification and characterization of novel receptors and their ligands and their mechanism of action. This knowledge translates to therapeutic use of these receptors in two opposing settings: to use agonists to dampen immune cell activation in inflammatory diseases or to use antagonists as anti-cancer treatment.
Meyaard entered the inhibitory receptor field during her post-doctoral stay in California by cloning a novel inhibitory receptor, LAIR-1. Back in Utrecht, our group was the first to identify collagens and collagen-like proteins as the natural ligands for LAIR-1. Our research extended towards other inhibitory receptors that are able to control collateral damage by the immune system and we discovered SIRL-1 as a novel inhibitory receptor able to regulate the function of neutrophils and monocytes. Recently, our lab found that SIRL-1 is a powerful inhibitor of potentially damaging functions of neutrophils, such as Neutrophil Extracellular Trap formation, while preserving other antimicrobial functions, making it an interesting target for inflammatory disease.
Using mouse models, we established an essential role for CD200R in the down-regulation of anti-tumor responses on the one hand and in the control of immune-mediated damage upon viral infections on the other hand. Furthermore, a translational research team with clinician Prof Dr Louis Bont was formed, studying regulation of neutrophilic airway inflammation and the potential to therapeutically exploit inhibitory receptors in this setting.
Testament to the growing global interest in targeting inhibitory receptors, are Meyaards collaborations with pharmaceutical and biotech companies. She is actively pursuing these options to translate her scholarly work into clinical application. In the context of cancer, our aim is to identify and characterize novel immunological checkpoints that limit anti-tumor responses. The mechanism of action of these receptors and the cells they control will provide basic insight into tumor immune surveillance and failing anti-tumor responses. This is essential for future development of novel immunological checkpoint blockade strategies that lead to elimination of cancer cells while causing minimal collateral damage.