A5018643031- Phagocytosis and Immune Regulation
- Immune cells in cancer
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Complement system in diseases
- Cell Adhesion Molecules Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Autophagy in Disease and Therapy
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Chemokine receptors and signaling
- HER2/EGFR in Cancer Research
- Platelet Disorders and Treatments
- Inflammatory Biomarkers in Disease Prognosis
- Erythrocyte Function and Pathophysiology
- DNA Repair Mechanisms
- Galectins and Cancer Biology
University of Amsterdam
2016-2021
Sanquin
2016-2021
Amsterdam University Medical Centers
2019
Amsterdam UMC Location University of Amsterdam
2016-2018
Leiden University Medical Center
2015
Highlights•Neutrophils kill antibody-opsonized cancer cells by a process called trogoptosis•Cancer cell plasma membrane ingestion neutrophils is instrumental in trogoptosis•Trogoptosis further enhanced CD47-SIRPα checkpoint inhibitionSummaryDestruction of therapeutic antibodies occurs, at least part, through antibody-dependent cellular cytotoxicity (ADCC), and this can be mediated various Fc-receptor-expressing immune cells, including neutrophils. However, the mechanism(s) which has not been...
Glycosylation of the immunoglobulin G (IgG)-Fc tail is required for binding to Fc-gamma receptors (FcγRs) and complement-component C1q. A variety IgG1 glycoforms detected in human sera. Several groups have found global or antigen specific skewing IgG glycosylation, example autoimmune diseases, viral infections, alloimmune reactions. The glycoprofiles seem correlate with disease outcome. Additionally, IgG-glycan composition contributes significantly Ig based therapies, as IVIg diseases...
Small ubiquitin-like modifiers play critical roles in the DNA damage response (DDR). To increase our understanding of SUMOylation mammalian DDR, we employed a quantitative proteomics approach order to identify dynamically regulated SUMO-2 conjugates and modification sites upon treatment with damaging agent methyl methanesulfonate (MMS). We have uncovered dynamic set 20 upregulated 33 downregulated conjugates, 755 sites, which 362 were MMS. In contrast yeast, where is centered on homologous...
The function of the low-affinity IgG-receptor FcγRIIIb (CD16b), which is uniquely and abundantly expressed on human granulocytes, not clear. Unlike other Fcγ receptors (FcγR), it a glycophosphatidyl inositol (GPI) -anchored molecule does have intracellular signaling motifs. Nevertheless, can cooperate with FcγR to promote phagocytosis antibody-opsonized microbes by neutrophils. Here we investigated role during antibody-dependent cellular cytotoxicity (ADCC) neutrophils towards solid cancer...
Abstract Abs of the IgG isotype are glycosylated in their Fc domain at a conserved asparagine position 297. Removal core fucose this glycan greatly increases affinity for FcγRIII, resulting enhanced FcγRIII-mediated effector functions. Normal plasma contains ∼94% fucosylated Abs, but alloantibodies against, example, Rhesus D (RhD) and platelet Ags frequently have reduced fucosylation that enhances pathogenicity. The increased functions been put to use various afucosylated therapeutic...
Abstract Therapeutic monoclonal antibodies (mAb), directed toward either tumor antigens or inhibitory checkpoints on immune cells, are effective in cancer therapy. Increasing evidence suggests that the therapeutic efficacy of these antigen–targeting mAbs is mediated—at least partially—by myeloid effector which controlled by innate immune-checkpoint interaction between CD47 and SIRPα. We others have previously demonstrated inhibiting CD47–SIRPα interactions can substantially potentiate...
The efficacy of cancer therapeutic antibodies varies considerably among patients. Anti-cancer act through different mechanisms, including antibody-dependent cellular cytotoxicity (ADCC) triggered via Fcγ receptors (FcγR). This phagocyte ADCC can be promoted by interference with CD47-SIRPα interactions, but the magnitude this enhancement also individuals. Both FcγR and SIRPα display considerable genetic variation, we investigated whether explains some variability in ADCC. Because linkage...
Antibody-mediated blood disorders ensue after auto- or alloimmunization against cell antigens, resulting in cytopenia. Although the mechanisms of destruction are same as immunotherapies targeting tumor cells, many factors still unknown. Antibody titers, for example, often do not strictly correlate with clinical outcome. Previously, we found C-reactive protein (CRP) levels to be elevated thrombocytopenic patients, correlating thrombocyte counts, and bleeding severity. Functionally, CRP...
Anti-CD20 antibodies such as rituximab are broadly used to treat B-cell malignancies. These can induce various effector functions, including immune cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Neutrophils ADCC toward solid cancer cells by trogoptosis, a cytotoxic mechanism known be dependent on trogocytosis. However, neutrophils seem incapable of killing rituximab-opsonized lymphoma cells. Nevertheless, do trogocytose cells, but this only reduces CD20 surface expression and...
<div>Abstract<p>Therapeutic monoclonal antibodies (mAb), directed toward either tumor antigens or inhibitory checkpoints on immune cells, are effective in cancer therapy. Increasing evidence suggests that the therapeutic efficacy of these antigen–targeting mAbs is mediated—at least partially—by myeloid effector which controlled by innate immune-checkpoint interaction between CD47 and SIRPα. We others have previously demonstrated inhibiting CD47–SIRPα interactions can...
<div>Abstract<p>Therapeutic monoclonal antibodies (mAb), directed toward either tumor antigens or inhibitory checkpoints on immune cells, are effective in cancer therapy. Increasing evidence suggests that the therapeutic efficacy of these antigen–targeting mAbs is mediated—at least partially—by myeloid effector which controlled by innate immune-checkpoint interaction between CD47 and SIRPα. We others have previously demonstrated inhibiting CD47–SIRPα interactions can...
<p>Supplementary Materials and Methods</p>
<p>Supplementary Materials and Methods</p>
<p>Supplementary Figures</p>
<p>Supplementary Figures</p>