- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Autoimmune and Inflammatory Disorders Research
- Single-cell and spatial transcriptomics
- Cancer Cells and Metastasis
- Cell Image Analysis Techniques
- Cytomegalovirus and herpesvirus research
- Renal and related cancers
- Herpesvirus Infections and Treatments
- Glioma Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Rheumatoid Arthritis Research and Therapies
- Diabetes and associated disorders
- Advanced Fluorescence Microscopy Techniques
- Food Allergy and Anaphylaxis Research
- Chemical Reactions and Isotopes
- Immune Response and Inflammation
- Immunodeficiency and Autoimmune Disorders
- Reproductive System and Pregnancy
- Genetic and Kidney Cyst Diseases
- SARS-CoV-2 and COVID-19 Research
- Inflammasome and immune disorders
- Cancer, Hypoxia, and Metabolism
Princess Máxima Center
2020-2024
Oncode Institute
2019-2024
University of California, San Diego
2016-2023
Cancer Genomics Centre
2020
Wilhelmina Children's Hospital
2009-2015
University Medical Center Utrecht
2009-2015
Discovery Institute
2010
Sanford Burnham Prebys Medical Discovery Institute
2010
Utrecht University
2007
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...
Organoid technology, in vitro 3D culturing of miniature tissue, has opened a new experimental window for cellular processes that govern organ development and function as well disease. Fluorescence microscopy played major role characterizing their composition detail demonstrating similarity to the tissue they originate from. In this article, we present comprehensive protocol high-resolution imaging whole organoids upon immunofluorescent labeling. This method is widely applicable differing...
During a microbial infection, responding CD8+ T cells give rise to effector that provide acute host defense and memory sustained protection. An alternative outcome is exhaustion, state of cell dysfunction occurs in the context chronic infections cancer. Although it evident exhausted (TEX) are phenotypically molecularly distinct from cells, factors regulating earliest events differentiation process TEX remain incompletely understood. Here, we performed single-cell RNA-sequencing...
Naturally occurring CD4+CD25+ regulatory T cells (Tregs) play a critical role in the maintenance of self-tolerance and it has been suggested that these Tregs may also be involved preventing allergic disease.The precise regulation responses to mucosal antigens remains elucidated. In present study, was investigated whether are induction oral tolerance they controlling hypersensitivity food proteins.CD4+CD25+ were depleted with PC61 mAb before low dose peanut extract (PE). addition, cell...
Dendritic cells are believed to play an essential role in regulating the balance between immunogenic and tolerogenic responses mucosal Ags by controlling T cell differentiation activation via costimulatory coinhibitory signals. The CD28/CTLA-4-CD80/CD86 signaling pathway appears be one of most important regulators but its exact orally administered proteins remains elucidated. In present study, involvement induction allergic sensitization oral tolerance peanut was investigated. both...
Suppression of CD8 and CD4 T cells is a hallmark in chronic viral infections, including hepatitis C HIV. While multiple pathways are known to inhibit cells, the host molecules that restrict cell responses less understood. Here, we used inducible cell-specific deletion gene encoding TGF-β receptor during lymphocytic choriomeningitis virus infection mice, determined signaling restricted proliferation terminal differentiation antiviral cells. also inhibited cytotoxic program includes granzymes...
To determine whether therapeutic strategies that block interleukin-6 (IL-6) or tumor necrosis factor α (TNFα) can improve the responsiveness of Teff cells to suppression in patients with juvenile idiopathic arthritis (JIA).Synovial fluid mononuclear (SFMCs) from inflamed joints JIA were cultured presence etanercept anti-IL-6 vitro, and protein kinase B (PKB)/c-Akt activation measured. In addition, vivo effects TNFα blockade investigated using peripheral blood obtained before after start...
Chronic viral infections represent a major challenge to the host immune response, and unique network of immunological elements, including cytokines, are required for their containment. By using model persistent infection with natural murine pathogen lymphocytic choriomeningitis virus clone 13 (LCMV Cl13) we investigated role one such cytokine, interleukin-27 (IL-27), in control chronic infection. We found that IL-27 receptor (IL-27R) signaling promoted LCMV Cl13 as early days 1 5 after...
Objective Resistance of Teff cells to Treg cell–mediated suppression contributes the breakdown peripheral tolerance in inflamed joints patients with juvenile idiopathic arthritis (JIA). However, unanswered questions are whether this resistant phenotype is self‐sustained and CD8+ CD4+ share same mechanism resistance suppression. We undertook study investigate intrinsic determine how can be targeted therapeutically. Methods or were cultured without antigen‐presenting (APCs) cell–dependent...
The role of IL-27 in antiviral immunity is still incompletely understood, especially the context chronic viruses that induce a unique environment their infected host. Cytomegalovirus (CMV) establishes persistent, tissue localized infection followed by lifelong latency. CMV infects majority people and although asymptomatic healthy individuals, can cause serious disease or death those with naïve compromised immune systems. Therefore, there an urgent need to develop protective vaccine for...
Abstract Neuroblastoma resection represents a major challenge in pediatric surgery, because of the high risk complications. Fluorescence-guided surgery (FGS) could lower this by facilitating discrimination tumor from normal tissue and is gaining momentum adult oncology. Here, we provide first molecular-targeted fluorescent agent for FGS oncology, developing preclinically evaluating GD2-specific tracer consisting immunotherapeutic antibody dinutuximab-beta, recently approved neuroblastoma...
Background CD4+CD25+FOXP3+ Regulatory T cells (Treg) play a central role in the immune balance to prevent autoimmune disease. One outstanding question is how Tregs suppress effector responses human. Experiments mice demonstrated that Treg restrict cell (Teff) by deprivation of growth factor IL-2 through consumption, resulting apoptosis Teff. Principal Findings In this study we investigated relevance Teff induction human function. To end, studied naturally occurring (nTreg) from peripheral...