A5021440888- Immunotherapy and Immune Responses
- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- Immune Cell Function and Interaction
- Carbohydrate Chemistry and Synthesis
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Radiopharmaceutical Chemistry and Applications
- Clusterin in disease pathology
- vaccines and immunoinformatics approaches
- Ferroptosis and cancer prognosis
- Toxin Mechanisms and Immunotoxins
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Cancer Cells and Metastasis
- Tannin, Tannase and Anticancer Activities
- Metabolism, Diabetes, and Cancer
- Immune Response and Inflammation
- Medical Imaging Techniques and Applications
- Neuroinflammation and Neurodegeneration Mechanisms
- Glioma Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Erythrocyte Function and Pathophysiology
Radboud University Nijmegen
2021-2025
Radboud University Medical Center
2021-2025
University Medical Center
2016-2024
Radboud Institute for Molecular Life Sciences
2021-2022
Amsterdam University Medical Centers
2018-2020
Vrije Universiteit Amsterdam
2018-2020
Amsterdam UMC Location Vrije Universiteit Amsterdam
2016-2018
University Hospital and Clinics
2016
Sialic acids are negatively charged nine-carbon carboxylated monosaccharides that often cap glycans on glycosylated proteins and lipids. Because of their strategic location at the cell surface, sialic contribute to interactions critical for immune homeostasis via with acid-binding Ig-type lectins (siglecs). In particular, these may be importance in cases where overexpressed, such as certain pathogens tumors. We now demonstrate modification antigens (Sia-antigens) regulates generation...
// Maurizio Perdicchio 1, 4 , Lenneke A. M. Cornelissen 1 Ingeborg Streng-Ouwehand Steef Engels Marleen I. Verstege Louis Boon 2 Dirk Geerts 3 Yvette van Kooyk * Wendy W. J. Unger 5, Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands EPIRUS Biopharmaceuticals, Leiden, Pediatric Oncology/Hematology, Erasmus Rotterdam, Clinical Research Division, Fred Hutchinson Cancer Seattle, WA, USA 5 Pediatrics, Division Infectious Diseases,...
Glioblastoma is the most aggressive brain malignancy, for which immunotherapy has failed to prolong survival. Glioblastoma-associated immune infiltrates are dominated by tumor-associated macrophages and microglia (TAMs), key mediators of suppression resistance immunotherapy. We others demonstrated aberrant expression glycans in different cancer types. These trigger inhibitory signaling TAMs through glycan-binding receptors. investigated glioblastoma glycocalyx as a tumor-intrinsic...
Expression of the tumor-associated glycan Tn antigen (αGalNAc-Ser/Thr) has been correlated to poor prognosis and metastasis in multiple cancer types. However, exact mechanisms exerted by support tumor growth are still lacking. One emerging hallmark is evasion immune destruction. Although cells often exploit glycosylation machinery interact with system, contribution an immunosuppressive microenvironment scarcely studied. Here, we explored how influences cell composition a colorectal (CRC)...
Sialic acids are negatively charged carbohydrates that cap the glycans of glycoproteins and glycolipids. involved in various biological processes including cell-cell adhesion immune recognition. In dendritic cells (DCs), major antigen-presenting system, sialic emerge as important regulators maturation interaction with other lymphocytes T cells. Many aspects how regulate DC functions not well understood tools model systems to address these limited. Here, we have established cultures murine...
Sialylated glycan structures are known for their immunomodulatory capacities and contribution to tumor immune evasion. However, the role of aberrant sialylation in colorectal cancer consequences complete desialylation on anti-tumor immunity remain unstudied. Here, we report that CRISPR/Cas9-mediated knock out CMAS gene, encoding a key enzyme pathway, mouse MC38 cell line completely abrogated surface expression sialic acids (MC38-Sianull ) and, unexpectedly, significantly increased vivo...
The T cell is an immune subset highly effective in eliminating cancer cells. Cancer immunotherapy empowers cells and occupies a solid position treatment. response rate, however, remains relatively low (<30%). efficacy of dependent on infiltration into the tumor microenvironment (TME) ability these infiltrated to sustain their function within TME. A better understanding inhibitory impact TME crucial improve immunotherapy. Tumor are well described for switch aerobic glycolysis (Warburg...
Saponin-based adjuvants (SBAs) distinguish themselves as vaccine by instigating a potent activation of CD8+ T cells. Previously, we discovered SBA's ability to induce cross-presentation in dendritic cells (DCs) leading cell activation. Moreover, the MHCIIloCD11bhi bone marrow-derived DC (BMDC) subset was identified be most responsive SBA treatment. To further investigate mode action, labeling SBAs optimized with fluorescent dye SP-DiIC18(3). Efficient uptake occurs specifically BMDCs and...
Abstract Aberrant fucosylation in cancer cells is considered as a signature of malignant cell transformation and it associated with tumor progression, metastasis resistance to chemotherapy. Specifically, colorectal cells, increased levels the fucosylated Lewisx antigen are attributed deregulated expression pertinent fucosyltransferases, like fucosyltransferase 4 (FUT4) 9 (FUT9). However, lack experimental models closely mimicking cancer-specific regulation gene has, so far, limited our...
Antigen uptake by dendritic cells and intracellular routing of antigens to specific compartments is regulated C-type lectin receptors that recognize glycan structures. We show the modification Ovalbumin (OVA) with glycan-structure Lewis(X) (Le(X)) re-directs OVA receptor MGL1. Le(X)-modification favored Th1 skewing CD4(+) T enhanced cross-priming CD8(+) cells. While cross-presentation native requires high antigen dose TLR stimuli, Le(X) reduces required amount 100-fold obviates its...
Tumors create an immunosuppressive tumor microenvironment by altering protein expression, but also changing their glycosylation status, like altered expression of sialoglycans. Sialoglycans are capped with sialic acid sugar residues and recognized Siglec immune receptors. Siglec-7 is inhibitory receptor similar to PD-1, emerging as glycoimmune checkpoint exploited cancer cells evade the system. However, exact cellular molecular conditions required for Siglec-7-mediated cell inhibition remain...
Abstract Myeloid cells, crucial players in antitumoral defense, are affected by tumor-derived factors and treatment. The role of myeloid cells their progenitors prior to tumor infiltration is poorly understood. Here we show single-cell transcriptomics functional analyses the cell lineage patients with non-medullary thyroid carcinoma (TC) multinodular goiter, before after treatment radioactive iodine compared healthy controls. Integrative data analysis indicates that monocytes TC have...
The tumor microenvironment of glioblastoma IDH-wildtype is highly immune suppressive and characterized by a strong component myeloid-derived suppressor cells (MDSCs). To interfere with the functions MDSCs, comprehensive understanding on how MDSCs acquire their phenotype essential. Previously, we others have shown distinct Sialic acid-binding immunoglobulin-like lectin (Siglec) receptor expression profile for in glioblastoma. Siglec receptors can transmit inhibitory signals comparable to PD-1...
Abstract Objectives PD‐1/PD‐L1 immune checkpoint blockade can be an effective treatment for advanced breast cancer patients. However, patients with oestrogen receptor positive (ER+) tumors often display only low lymphocyte infiltration, while a large part of triple negative (TN) does not generate immunotherapy response. Therefore, new strategies have to developed. Here, we investigate Siglec‐7 and Siglec‐9 as novel ITIM‐bearing inhibitory receptors similar PD‐1, but expressed on broader...
Abstract Many immunotherapies focus on (re)invigorating CD8 + T cell anti-cancer responses and different nuclear imaging techniques have been developed to measure distributions. In vivo labeling approaches using radiotracers primarily show distributions, while ex labeled cells can migration patterns, homing, tumor infiltration. Currently, a comprehensive head-to-head comparison of in ex-vivo with respect their normal tissue targeting properties correlation the presence is lacking, yet...
Abstract The tumor microenvironment is immune suppressive, allowing cells to escape from attack. By relieving this suppression, might be able effectively eliminate the tumor. Therefore, a detailed understanding on how induce an immunosuppressive required. Glycosylation most abundant post-translational modification of proteins. It highly diverse cellular level and strongly affected by oncogenesis. Tumor generally display aberrant glycosylation profile now well accepted as new hallmark cancer....