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The PhD position bridges Research Programs of the two Medical Priorities Immunotherapy and Immunity & Inflammation, consisting of several PhD students and technical support within Sanquin. The project investigates the role of neutrophils and complement activation in cancer. Although numerous data support a pro-tumor role of activated neutrophils as so-called myeloid derived suppressor (MDSC) activity, the role of complement in cancer has been less well studied, and the interaction within the tumor microenvironment (TME) between these two pillars of innate immunity is totally unclear.
The position
The PhD student will investigate the presence of activated neutrophils and complement proteins within tissue sections of various tumors by state-of-the art multicolor confocal laser scanning microscopy (CLSM Airy2-can), and determine the contribution of local complement production, activation and regulation by cells in the TME, or extravasation of complement proteins from plasma into the TME. Since in many studies the TME is believed to be low in oxygen, we will study how hypoxia might influence MDSC activity, complement activation and complement regulation on the cells to give insight into how these processes may impact innate immunity within the TME landscape as well. Various techniques will be used, including ELISA’s, PCRs, functional characterization of antibodies, cell culture, complement and neutrophil activity tests, and multi-color flow-cytometry and imaging.
Research group
Over the last two years, the neutrophil research and the complement research groups of Sanquin have worked together with the clinical oncology and pathology departments at the National Cancer Institute (Dr. Jan Paul de Boer; Antoni van Leeuwenhoek, NKI). The PhD student will be part of both research groups at Sanquin while working closely together with the NKI, benefiting from the specific expertise of each member. The ground work on studying the TME immune landscape at the Imaging Center at Sanquin makes it possible to now proceed and answer the research question on complement within the TME. Evidence obtained can lead to the application of complement blocking agents to improve the efficacy and success of current immunotherapies in the treatment of solid cancers further.
The mission of Sanquin is: “Together with the donor we ensure a better life for patients”. Sanquin is a knowledge-driven not-for-profit organization that supplies life-saving products and services, as well as involved in blood transfusion medicine- and immunology-related research.
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