This work has described synthetic strategies towards well-defined structures resembling capsular polysaccharide (CPS) fragments, CPS mimics, teichoic acid (TA) fragments as well as a third... Show moreThis work has described synthetic strategies towards well-defined structures resembling capsular polysaccharide (CPS) fragments, CPS mimics, teichoic acid (TA) fragments as well as a third-generation ring-closing tandem metathesis (RCM) linker to better exploit the potential of automated synthesis. The synthesis of diheteroglycan (DHG) fragments of the Gram-positive Enterococcus faecalis have been described and preliminary biological properties shown. CPS-mimics of Neisseria meningitidis A, a Gram-negative bacterium and one of the major causes of bacterial meningitis, could provide an alternative to the inherent instability of current glycoconjugate vaccines. TA fragments presented in this thesis, typical for Gram-positive bacteria, have been equipped with labile D-alanine appendages to further investigate their biological relevance in interactions with the host immune system. A tandem-RCM linker has been developed and tested on a carbohydrate automated synthesizer, providing a proof of concept of its use. Show less
Kidney transplantation is the best treatment option for patients with kidney failure. Unfortunately many patients lose their allograft due to (chronic) rejection. Rejection is caused by the immune... Show moreKidney transplantation is the best treatment option for patients with kidney failure. Unfortunately many patients lose their allograft due to (chronic) rejection. Rejection is caused by the immune reaction of the recipient against the donor’s human leukocyte antigens (HLA). While traditional kidney allocation is based on HLA matching on the antigen level, matching on the epitope level could be more feasible. Furthermore, epitope mismatch analysis could be used for post-transplant risk stratification, enabling the personalisation of immunosuppressive treatment for kidney transplant recipients. In this thesis, the basic science and clinical application of HLA epitopes in kidney transplantation are discussed. Show less
Colorectal cancer is one of the most diagnosed cancer types worldwide and incidence remains on the rise, especially in patients under 50. The prognosis for patients with CRC differs greatly and... Show moreColorectal cancer is one of the most diagnosed cancer types worldwide and incidence remains on the rise, especially in patients under 50. The prognosis for patients with CRC differs greatly and although immunotherapy has shown promising results in a number of cancer types, not all CRC patients respond well to these treatments. This can in part be attributed to the differences in T cell infiltration between cancers but does not one on one translate to clinical response. Moreover, the activity of specific immune cells can directly influence other immune cells, both in an activating and inhibitory manner. This highlights the complexity of the tumour immune microenvironment and requires an comprehensive multiplex approach to simultaneously investigate all the players of the tumour immune microenvironment. Furthermore, the interaction between different immune cells and between those and cancer cells is essential to take into account, hence the need for an approach that combines multiplex immunophenotyping with spatial cell context. This will provide hints into the behaviour of the players of the tumour immune microenvironment and aid the understanding of CRC, but potentially of other cancer types as well. In this work we developed and applied multispectral immunophenotyping methodologies to strengthen our understanding of CRC Show less
