A5087282255- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- RNA modifications and cancer
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Cancer Immunotherapy and Biomarkers
- Immune Response and Inflammation
- Circular RNAs in diseases
- Hematopoietic Stem Cell Transplantation
- vaccines and immunoinformatics approaches
- Virus-based gene therapy research
- MicroRNA in disease regulation
- interferon and immune responses
- Single-cell and spatial transcriptomics
- Neuroinflammation and Neurodegeneration Mechanisms
- Chemokine receptors and signaling
- RNA regulation and disease
- Renal cell carcinoma treatment
- Neonatal Respiratory Health Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- RNA and protein synthesis mechanisms
- Immune cells in cancer
- Cytomegalovirus and herpesvirus research
Sanquin
2015-2024
Amsterdam University Medical Centers
2018-2024
Oncode Institute
1999-2024
University of Amsterdam
2014-2024
Cancer Center Amsterdam
2024
The Netherlands Cancer Institute
1999-2019
Amsterdam UMC Location University of Amsterdam
1997-2018
La Jolla Institute for Immunology
2006-2011
Clinical implementation of tumor organoids for personalized medicine requires that pure can be reliably established. Here, we present our experience with organoid cultures from >70 non-small cell lung cancer (NSCLC) samples. We systematically evaluate several methods to identify purity established intrapulmonary tumors. Eighty percent lesions have a normal copy number profile, suggesting overgrowth by airway (AOs). This is further supported the failure detect mutations found in original...
Activated CD8+ T cells detect virally infected and tumor by recognition of major histocompatibility complex class I-bound peptides derived from degraded, endogenously produced proteins. In contrast, cell activation often occurs through interaction with specialized antigen-presenting displaying acquired an exogenous cellular source, a process termed cross-priming. Here, we observed marked inefficiency in presentation epitopes signal sequences mouse models. These data indicate that certain...
Hematopoietic stem cells differentiate into a broad range of specialized blood cells. This process is tightly regulated and depends on transcription factors, micro-RNAs, long non-coding RNAs. Recently, also circular RNA (circRNA) were found to regulate cellular processes. Their expression pattern their identity however less well defined. Here, we provide the first comprehensive analysis circRNA in human hematopoietic progenitors, differentiated lymphoid myeloid We here show that cell-type...
Cytotoxic CD8 + T cells can effectively kill target by producing cytokines, chemokines, and granzymes. Expression of these effector molecules is however highly divergent, tools that identify preselect with a cytotoxic expression profile are lacking. Human be divided into IFN-γ– IL-2–producing cells. Unbiased transcriptomics proteomics analysis on cytokine-producing fixed revealed IL-2 produce helper IFN-γ molecules. expressed the surface marker CD29 already prior to stimulation. also marked...
Vagal nerve efferent activation has been shown to ameliorate the course of many inflammatory disease states. This neuro-modulatory effect suggested rest on acetylcholine receptor (AChR) tissue macrophages or dendritic cells (DCs). In more recent studies, vagal anti-inflammatory activity was involve adrenergic, splenic, pathways. Here we provide evidence that rather than cholinergic, bone marrow derived DCs results in enhanced endocytosis uptake, IL-10 production but a decreased IL-6,...
Significance A hallmark of effective T cell responses against invading pathogens is the production effector molecules. Effector molecules such as cytokines not only kill infected cells, but they also recruit innate immune cells and alter environment to optimally respond microbial infections. However, because are very potent, can pose a health risk. When produced excessively or when generated at wrong time, this aberrant induce immunopathology. Here, we uncover that each cytokine employs...
CD8(+) T cells can respond to unrelated infections in an Ag-independent manner. This rapid innate-like immune response allows Ag-experienced alert other cell types pathogenic intruders. In this study, we show that murine sense TLR2 and TLR7 ligands, resulting production of IFN-γ but not TNF-α IL-2. Importantly, activated by TLR ligands produce sufficient augment the activation macrophages. contrast Ag-specific reactivation, TLR-dependent relies exclusively on newly synthesized transcripts...
T cells are key players in our defence against infections and malignancies. When differentiate or become activated, they undergo substantial alterations gene expression. Even though RNA expression levels now well documented throughout different stages of cells, it is not understood how mRNA translates into the protein landscape. By combining paired sequencing mass spectrometry data primary human CD8 + we report that a poor proxy for overall output, irrespective differentiation activation...
Potent T cell responses against infections and malignancies require a rapid yet tightly regulated production of toxic effector molecules. Their level is defined by post-transcriptional events at 3′ untranslated regions (3′ UTRs). RNA binding proteins (RBPs) are key regulators in this process. With an aptamer-based capture assay, we identify >130 RBPs interacting with IFNG, TNF, IL2 UTRs human cells. RBP-RNA interactions show plasticity upon activation. Furthermore, uncover the intricate...
The role of memory T cells during the immune response against random antigenic variants has not been resolved. Here, we show by simultaneous staining with two tetrameric major histocompatibility complex (MHC)-peptide molecules, that polyclonal CD8(+) cell a series natural influenza A nucleoprotein epitope is completely dominated infrequent cross-reactive expand from an original population. Based on both biochemical and functional criteria, these cytotoxic productively recognize parental...
Optimal T cell activation requires Ag recognition through the TCR, engagement of costimulatory molecules, and cytokines. cells can also directly recognize danger signals expression TLRs. Whether TLR ligands have capacity to provide enhance Ag-driven is not well understood. In this study, we show that TLR2 TLR7 potently lower threshold for cytokine production in cells. To investigate how triggering supports production, adapted protocol flow cytometry-based fluorescence situ hybridization...
Abstract Effective T cell responses entail the coproduction of IFN-γ, TNF-α, and IL-2. Cytokine production is determined by transcriptional posttranscriptional events. However, increased transcript levels do not always translate into protein production, therefore simultaneous transcripts measurement are essential for appropriate analysis responses. In this study, we optimized flow cytometry–based fluorescence in situ hybridization (Flow-FISH) IFN-γ to multicolor cytometry that allows...
High-risk pediatric neuroblastoma patients have a dismal survival rate despite intensive treatment regimens. New options are thus required. Even though HLA expression in is low and immune cell infiltrates limited, the presence of tumor infiltrating lymphocytes (TILs) indicative for better patient survival. Here, we show that most lesions contain viable after induction chemotherapy, with high percentages CD3+ T cells. We therefore expanded TILs tested their anti-tumoral activity. With...
In a local immune response, the priming and expansion of antigen-specific T cell population has been thought to largely take place in draining lymphoid tissue. This model was primarily based on indirect enumeration cells by limiting dilution analyses. Here, tetrameric MHC class I complexes were used evaluate contribution different secondary organs response following CD8+ responses against immunodominant epitopes influenza A virus herpes simplex virus-1. Mice either intranasally infected with...
Protective T cell responses against tumors require the production of Interferon gamma (IFN-γ). However, tumor-infiltrating cells (TILs) gradually lose their capacity to produce IFN-γ and therefore fail clear malignant cells. Dissecting underlying mechanisms that block cytokine is thus key for improving products. Here we show although TILs express substantial levels Ifng mRNA, post-transcriptional impede protein due loss mRNA stability. CD28 triggering, but not PD1 blocking antibodies,...
Non-small cell lung cancer (NSCLC) is the second most prevalent type of cancer. With current treatment regimens, mortality rate remains high. Therefore, better therapeutic approaches are necessary. NSCLCs generally possess many genetic mutations and well infiltrated by T cells (TIL), making TIL therapy an attractive option. Here we show that from naive, stage I-IVa NSCLC tumors can effectively be isolated expanded, with similar efficiency as normal tissue. Importantly, 76% (13/17) tested...