A5052876085- Immune Cell Function and Interaction
- Cell death mechanisms and regulation
- Cell Adhesion Molecules Research
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- NF-κB Signaling Pathways
- Cellular transport and secretion
- Extracellular vesicles in disease
- Immune Response and Inflammation
- RNA Interference and Gene Delivery
- Cytomegalovirus and herpesvirus research
- Immunotherapy and Immune Responses
- Phagocytosis and Immune Regulation
- Galectins and Cancer Biology
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Toxoplasma gondii Research Studies
- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
- Lymphoma Diagnosis and Treatment
- Signaling Pathways in Disease
- Calcium signaling and nucleotide metabolism
- Acute Lymphoblastic Leukemia research
University Hospital Schleswig-Holstein
2015-2024
University of Lübeck
2015-2024
Kiel University
2013-2023
Institute of Immunology
2015-2017
Clinical Research Center Kiel
2005-2015
The interaction of the MHC class I-related chain molecules A and B (MICA MICB) with corresponding natural killer group 2, member D (NKG2D) receptor triggers cytotoxic effector activity cells certain T-cell subsets provides a costimulatory signal for cytokine production. Thus, presence MICA/B on transformed contributes to tumor immunosurveillance. Consequently, proteolytic cleavage is regarded as an important immune escape mechanism various cancer cells. To investigate molecular machinery...
Nck is a ubiquitously expressed adapter protein that almost exclusively built of one SH2 domain and three SH3 domains. The two isoproteins are functionally redundant in many aspects differ only few amino acids mostly located the linker regions between interaction modules. proteins connect receptor non-receptor tyrosine kinases to machinery actin reorganisation. Thereby, regulates activation-dependent processes during cell polarisation migration plays crucial role signal transduction variety...
The interaction of the MHC class I-related chain molecules A and B (MICA MICB) UL-16 binding protein (ULBP) family members expressed on tumor cells with corresponding NKG2D receptor triggers cytotoxic effector functions in NK γδ T cells. However, as a mechanism immune escape, ligands (NKG2DLs) can be released from cell surface. In this study, we investigated NKG2DL system different human glioblastoma (GBM) lines, most lethal brain adults. Flow cytometric analysis ELISA revealed that despite...
TGF-β is a pleiotropic cytokine with multiple roles in immunity. Apart from its suppressive activity, driving the differentiation of induced regulatory T cells (iTreg) but also polarization interleukin-9 (IL-9) producing helper 9 (Th9) cells. Human Vδ2 expressing γδ exert potent cytotoxicity towards variety solid tumor and leukemia/lymphoma target thus are focus current strategies to develop cell-based immunotherapies. Here we report that unexpectedly augments cytotoxic effector activity...
Despite aggressive treatment regimens based on surgery and radiochemotherapy, the prognosis of patients with grade IV glioblastoma multiforme (GBM) remains extremely poor, calling for alternative options such as immunotherapy. Immunological mechanisms including Natural Killer Group 2 member D (NKG2D) receptor-ligand system play an important role in tumor immune surveillance targeting NKG2D might be beneficial. However, before considering any kind immunotherapy, a precise characterization is...
Human Vγ9Vδ2 T cells recognize in a butyrophilin 3A/CD277-dependent way microbial (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) or endogenous pyrophosphates (isopentenyl [IPP]). Nitrogen-bisphosphonates such as zoledronic acid (ZOL) trigger selective γδ cell activation because they stimulate IPP production monocytes by inhibiting the mevalonate pathway downstream of synthesis. We performed comparative analysis capacity purified monocytes, neutrophils, and CD4 to serve accessory for...
Abstract Ovarian cancer (OvCa) is the gynaecological disorder with poorest prognosis due to fast development of chemoresistance. We sought connect chemoresistance and cell‐derived extracellular vesicles (EV). The mechanisms how sustained by EV remained elusive. One potentially contributing factor A Disintegrin Metalloprotease 17 (ADAM17)—itself being able promote inducing tumour cell proliferation survival via Epidermal Growth Factor Receptor (EGFR) pathway shedding several its ligands...
The tumor necrosis factor family member Fas ligand (FasL) induces apoptosis in receptor-expressing target cells and is an important cytotoxic effector molecule used by CTL- NK-cells. In these hematopoietic cells, newly synthesized FasL stored specialized secretory lysosomes only delivered to the cell surface upon activation recognition. contains 80-amino acid-long cytoplasmic tail, which includes a proline-rich domain as bona fide Src homology 3 domain-binding site. This has been implicated...
The Fas ligand (FasL) is a key death factor of cytotoxic T lymphocytes and natural killer cells. It stored intracellularly as transmembrane protein secretory lysosomes. Upon activation, these vesicles are transported to the immunological synapse (IS), FasL becomes exposed cell surface trigger through ligation its receptor (CD95) on target cell. We propose that FasL-associated adaptor Nck involved in actin-dependent transport FasL-bearing lysosomes IS. binds proline-rich portion alters...
Abstract Nck is a ubiquitously expressed, primarily cytosolic adapter protein consisting of one SH2 domain and three SH3 domains. It links receptor nonreceptor tyrosine kinases to actin cytoskeleton reorganizing proteins. In T lymphocytes, crucial component signaling pathways for cell activation effector function. recruits remodeling proteins (TCR)‐associated clusters thereby initiates changes in polarity morphology. Moreover, the TCR‐induced mobilization secretory vesicles cytotoxic...
Cytotoxic T cells mobilize effector proteins from prestored lysosomal compartments. Since different activation signals result in alternative routes of target cell killing, utilizing either FasL or the granzyme B/perforin pathway, existence distinct forms granules was recently suggested. Applying a protocol for separation intact organelles activated lymphoblasts, we noticed that FasL-associated secretory lysosomes (SL) segregate vesicles containing larger amounts granzymes and granulysin. We...
Ligands for Stimulator of Interferon Genes (STING) receptor are under investigation as adjuvants in cancer therapy. Multiple effects have been described, including induction immunogenic cell death and enhancement CD8 T-cell mediated anti-tumor immunity. However, the potential STING ligands on activation effector functions tumor-reactive human γδ T cells not yet investigated. We observed that cyclic dinucleotide well novel non-dinucleotide diABZI MSA-2 co-stimulated cytokine Vδ2 within...
The TNF superfamily member Fas ligand acts as a prototypic death factor. Due to its ability induce apoptosis in (APO-1, CD95) expressing cells, participates essential effector functions of the immune system. It is involved natural killer cell- and T cell-mediated cytotoxicity, establishment privilege, termination responses by induction activation-induced cell death. In addition, ligand-positive tumours may evade surveillance killing Fas-positive tumour-infiltrating cells. Given these strong...
The a disintegrin and metalloproteases (ADAMs) play pivotal role in the control of development, adhesion, migration, inflammation cancer. Although numerous substrates ADAM10 have been identified, regulation its surface expression proteolytic activity is still poorly defined. One current hypothesis that both processes are part modulated by protein-protein interactions mediated intracellular portion protease. For related proteases, especially proline-rich regions serving as docking sites for...
Abstract Background Cytotoxic cells of the immune system have evolved a lysosomal compartment to store and mobilize effector molecules. In T lymphocytes NK cells, death factor FasL is one characteristic marker proteins these so-called secretory lysosomes, which combine properties conventional lysosomes exocytotic vesicles. Although vesicles are crucial for function, their protein content in has so far not been investigated detail. Results present study, intact membranous were enriched from...
The functional plasticity and anti-tumor potential of human γδ T cells have been widely studied. However, the epigenetic regulation T-cell/tumor cell interactions has poorly investigated. In present study, we show that treatment with histone deacetylase inhibitor Valproic acid (VPA) significantly enhanced expression and/or release NKG2D ligands MICA, MICB ULBP-2, but not ULBP-1 in pancreatic carcinoma line Panc89 prostate PC-3. Under vitro tumor co-culture conditions, full length truncated...
Pancreatic ductal adenocarcinoma (PDAC) is characterized by an immunosuppressive tumor microenvironment with a dense desmoplastic stroma. The expression of β-galactoside-binding protein galectin-3 regarded as intrinsic escape mechanism for inhibition tumor-infiltrating T cell function. In this study, we demonstrated that expressed PDAC and γδ or αβ cells but only released in small amounts either population. Interestingly, large were during the co-culture allogeneic vitro expanded autologous...
Cancer vaccinations sensitize the immune system to recognize tumor-specific antigens de novo or boosting preexisting responses. Dendritic cells (DCs) are regarded as most potent antigen presenting (APCs) for induction of (cancer) antigen-specific CD8+ T cell Chitosan nanoparticles (CNPs) used delivery vehicle have been shown improve anti-tumor This study aimed at exploring potential CNPs by assessing activation and expansion DCs subsequent cell-mediated lysis pancreatic ductal adenocarcinoma...