This thesis identifies specific targets, illustrates the role of these targets, and explores personalized therapeutic possibilities to inhibit tumor growth by using new treatment strategies.... Show moreThis thesis identifies specific targets, illustrates the role of these targets, and explores personalized therapeutic possibilities to inhibit tumor growth by using new treatment strategies. And the thesis describes a new animal model for CM. A proper model can mimic the human disorder and provide opportunities for studying tumor biology, and for seeking novel effective therapies to inhibit the dissemination of malignant cells. Subsequently, the potential role of immune checkpoint molecules and the presence of HLA class I antigens are studied. New animal models and therapeutic targets will broaden our understanding of CM, and help us to develop better treatments for primary and metastatic CM, thus prolonging patients’ survival. Show less
The aim of this thesis was to develop tools to detect and quantify HLA-specific memory B cells in peripheral blood of HLA-immunized individuals and to assess the applicability of the newly... Show moreThe aim of this thesis was to develop tools to detect and quantify HLA-specific memory B cells in peripheral blood of HLA-immunized individuals and to assess the applicability of the newly developed assays in the setting of clinical transplantation. Transplant patients who have already made a defense response to the foreign HLA on donor organ have an increased risk of developing antibody-mediated rejection, which may adversely affect the survival of the graft. In diagnostic HLA laboratories, serum of the patients is tested for the presence of HLA-specific antibodies before and after transplantation. Serum HLA antibodies are produced by plasma cells located in the bone marrow however, memory B cells can also play a role in antibody production against the donor organ. So far, the role of these cells has been neglected in the diagnostics. The research conducted in my PhD thesis enabled us to develop methods to detect HLA-specific memory B cells. By this means, patients who may potentially harbor HLA-specific memory B cells such as repeat transplant candidates, women receiving transplants from their partner or child and patients undergoing desensitization treatments may benefit from the assays that are described in this PhD thesis. Show less
D'Orsogna, L.; Heuvel, H. van den; Kooten, C. van; Heidt, S.; Claas, F.H.J. 2017
