A5086290087- Hematopoietic Stem Cell Transplantation
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Acute Myeloid Leukemia Research
- Asthma and respiratory diseases
- Immunodeficiency and Autoimmune Disorders
- Acute Lymphoblastic Leukemia research
- Neuroblastoma Research and Treatments
- Dermatology and Skin Diseases
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- RNA Interference and Gene Delivery
- Immune Response and Inflammation
- Cytomegalovirus and herpesvirus research
- Virus-based gene therapy research
- Allergic Rhinitis and Sensitization
- Monoclonal and Polyclonal Antibodies Research
- Childhood Cancer Survivors' Quality of Life
- Blood disorders and treatments
- COVID-19 Clinical Research Studies
- Ubiquitin and proteasome pathways
- Lymphoma Diagnosis and Treatment
- Renal Transplantation Outcomes and Treatments
Princess Máxima Center
2018-2025
University Medical Center Utrecht
2016-2025
Center for Translational Molecular Medicine
2015-2025
Utrecht University
2015-2024
Heidelberg University
2015-2023
University Hospital Heidelberg
2015-2023
Misgav Ladach
2022
Universidad de Salamanca
2022
Memorial Sloan Kettering Cancer Center
2022
Radboud University Nijmegen
2005-2020
Tumor microenvironments feature immune inhibitory mechanisms that prevent T cells from generating effective antitumor responses. Therapeutic interventions aimed at disrupting these have been shown to enhance immunity, but they lack direct cytotoxic effects. Here, we investigated the effect of cancer chemotherapeutics on pathways. We observed exposure platinum-based markedly reduced expression cell molecule programmed death receptor-ligand 2 (PD-L2) both human DCs and tumor cells....
Extending the success of cellular immunotherapies against blood cancers to realm solid tumors will require improved in vitro models that reveal therapeutic modes action at molecular level. Here we describe a system, called BEHAV3D, developed study dynamic interactions immune cells and patient cancer organoids by means imaging transcriptomics. We apply BEHAV3D live-track >150,000 engineered T cultured with patient-derived, solid-tumor organoids, identifying 'super engager' behavioral cluster...
Background Poor prognosis in colon cancer is associated with a high content of cancer-associated fibroblasts (CAFs) and an immunosuppressive tumor microenvironment. The relationship between these two features incompletely understood. Here, we aimed to generate model system for studying the interaction cells CAFs their effect on immune-related cytokines T cell proliferation. Methods were isolated from liver metastases immortalized prolong lifespan improve robustness reproducibility....
Pediatric patients with high-risk neuroblastoma have poor survival rates and urgently need more effective treatment options less side effects. Since novel improved immunotherapies may fill this need, we dissect the immunoregulatory interactions in by single-cell RNA-sequencing of 24 tumors (10 pre- 14 post-chemotherapy, including 5 pairs) to identify strategies for optimizing immunotherapy efficacy. Neuroblastomas are infiltrated natural killer (NK), T B cells, immunosuppressive myeloid...
Abstract Background: Five fulfilled hemophagocytic lymphohistiocytosis (HLH)‐2004 criteria, and the HScore are widely used recommended by international expert consensus to diagnose secondary HLH. Both diagnostic scores have never been validated in heterogeneous patient cohorts of HLH patients. We aimed systematically optimize validate criteria using a multicenter approach. Methods: developed optimized our cohort critically ill patients as first step. next these new together with original...
Dendritic cells (DC) are professional antigen-presenting that play a pivotal role in the induction of immunity. Ex vivo-generated, tumour antigen-loaded mature DC currently exploited as cancer vaccines clinical studies. However, antigen loading and maturation directly vivo would greatly facilitate application DC-based vaccines. We formerly showed murine models radiofrequency-mediated destruction can provide an source for anti-tumour immunity, we explored herein. In this paper evaluate...
The brain is a specialized immune site representing unique tumor microenvironment. availability of fresh material for ex vivo analysis often limited because large parts many tumors are resected using ultrasonic aspiration. We analyzed aspirates as biosource to study suppressive mechanisms in 83 human tumors. Lymphocyte infiltrates tissues and were comparable with respect lymphocyte content viability. Applying aspirates, we detected massive infiltration CD4+FoxP3+CD25high CD127low regulatory...
Abstract The suppressive activity of regulatory T cells (Treg) has been implicated as an important factor limiting immune mediated destruction tumor cells. However, not much is known about the presence and function Treg within tumors. Here we show in a syngeneic murine glioma model time‐dependent accumulation CD4+FoxP3+ brain Further analysis revealed upregulation CD25, CTLA‐4, GITR CXCR4 on intratumoral during growth. Moreover, freshly isolated were highly when tested directly ex vivo ....
Abstract Dendritic cells (DC) are professional antigen-presenting that play a pivotal role in the induction of immunity. Ex vivo–generated, tumor antigen–loaded mature DC currently exploited as cancer vaccines clinical studies. However, antigen loading and maturation directly vivo would greatly facilitate application DC-based vaccines. We have previously shown situ destruction by ablative treatments efficiently delivers antigens for antitumor In this article, we show although 20% draining...
Abstract Introduction Dupilumab has recently been approved for the treatment of moderate to severe atopic dermatitis (AD) in adults. Daily practice data on dupilumab are scarce. Objective To study effect 16‐week with clinical response and serum biomarkers adult patients moderate‐severe AD daily practice. Methods Data were extracted from BioDay registry, a prospective multicenter registry. Sixteen‐week effectiveness was expressed as number achieving EASI‐50 (Eczema Area Severity Index) or...
Objective. To determine the genotype–phenotype association in patients with adenosine deaminase-2 (ADA2) deficiency due to identical homozygous R169Q mutations CECR1.
Purpose Increasing the number of hematopoietic stem and progenitor cells within an umbilical cord blood (UCB) graft shortens time to recovery after UCB transplantation. In this study, we assessed safety efficacy a that was expanded ex vivo in presence nicotinamide transplanted myeloablative conditioning as stand-alone stem-cell graft. Methods Thirty-six patients with hematologic malignancies underwent transplantation at 11 sites. Results The cumulative incidence neutrophil engraftment day 42...
BackgroundAtopic dermatitis (AD) is a highly heterogeneous disease, both clinically and biologically, whereas patients are still being treated according to "one-size-fits-all" approach. Stratification of into biomarker-based endotypes important for future development personalized therapies.ObjectiveOur aim was confirm previously defined serum patient clusters in new cohort with AD.MethodsA panel 143 biomarkers measured by using Luminex technology samples from 146 severe AD (median Eczema...
The addition of fludarabine to cyclophosphamide as a lymphodepleting regimen prior CD19 chimeric antigen receptor (CAR) T-cell therapy significantly improved outcomes in patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). Fludarabine exposure, previously shown be highly variable when dosing is based on body surface area (BSA), predictor for survival allogeneic hematopoietic cell transplantation (allo-HCT). Hence, we hypothesized that an optimal exposure might...
Patients with inborn errors of immunity (IEI) are at increased risk severe coronavirus disease-2019 (COVID-19). Effective vaccination against COVID-19 is therefore great importance in this group, but little known about the immunogenicity vaccines these patients.We sought to study humoral and cellular immune responses after mRNA-1273 adult patients IEI.In a prospective, controlled, multicenter study, 505 IEI (common variable immunodeficiency [CVID], isolated or undefined antibody...
Dupilumab, a mAb targeting IL-4 receptor alpha (IL-4Rα), markedly improves disease severity in patients with atopic dermatitis. However, the effect of IL-4Rα blockade on dynamics circulating skin-homing T cells, which are crucial players pathologic mechanism dermatitis, has not been studied yet. In addition, it remains unknown whether dupilumab treatment induces long-lasting T- and B-cell polarization. Therefore, we short- long-term effects expression T-cell cytokine production within total...